3,3-difluoroallylamines or salts thereof and pharmaceutical compositions comprising the same

ABSTRACT

The present technology provides 3,3-difluoroallylamines or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and uses thereof. The 3,3-difluoroallylamines or their pharmaceutically acceptable salts exhibit potent inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority to Korean PatentApplication No. 10-2018-0161725, filed Dec. 14, 2018, and Korean PatentApplication No. 10-2019-0137387, filed Oct. 31, 2019, the entirecontents of each of which are incorporated by reference herein in theirentirety.

FIELD

The present technology relates to 3,3-difluoroallylamines orpharmaceutically acceptable salts thereof having inhibitory activity onvascular adhesion protein (VAP-1), a process for the preparationthereof, a pharmaceutical composition comprising the same, and usesthereof.

BACKGROUND

Vascular adhesion protein-1 (VAP-1) is a semicarbazide-sensitive amineoxidase (SSAO), which is abundantly present in human plasma. VAP-1 is anectoenzyme comprising a short cytoplasmic tail, a single transmembranedomain, and an extracellular domain with large and high glycosylationcontaining the center of activity. In addition, VAP-1 exists not only asa membrane-bound form in the endothelium, but also as a soluble form inserums (soluble VAP-1, sVAP-1). This form was shown to be a productcleaved from the membrane-bound VAP-1, and appears to have similarproperties as the tissue-bound form. It has been also reported thatVAP-1 is normally stored in intracellular granules within endothelialcells, but when an inflammatory response is evoked in response toinflammatory stimuli, it is translocated onto the cell membrane, and itsexpression is upregulated, and therefore, it is expressed more stronglyin inflamed tissues than in normal tissues.

Substrates for VAP-1 include endogenous methylamine and aminoacetone aswell as some xenobiotic amines such as tyramine and benzylamine.

VAP-1 has two physiological functions: the first is amine oxidaseactivity stated earlier in this section, and the second is cell adhesionactivity. Due to these two activities, VAP-1 has been shown to play akey role in the leakage of inflammatory cells as it acts as an adhesionprotein for leukocytes in inflamed sites [Trends Immunol. (2001) 22:211]. VAP-1-deficient transgenic mice are healthy, develop normally, andfertile, and phenotypically normal, but exhibit a marked decrease in theinflammatory responses evoked in response to various inflammatorystimuli [Immunity. (2005) 22: 105].

In addition, inhibitory activity of VAP-1 in multiple animal models ofhuman diseases (e.g., carrageenan-induced paw inflammation,oxazolone-induced colitis, lipopolysaccharide-induced lung inflammation,collagen-induced arthritis, endotoxin-induced uveitis) by the use ofantibodies or small molecules has been shown to prevent leukocyte fromrolling, adhering, and leaking, and reduce levels of inflammatorycytokines and chemokines, thereby reducing the severity of the disease[Eur J Immunol. (2005) 35: 3119; J Pharmacol Exp Ther. (2005) 315: 553;Annu Rep Med Chem. (2007) 42: 229; FASEB J. (2008) 22: 1094].Inflammation is the first reaction of the immune system to infection orstimulus, and in such a process, the movement of leukocytes into thetissue through circulation is an important step. The leukocytes arefirst bound to adhesion proteins and then adhered to the endotheliumbefore they start to pass through blood vessel walls. VAP-1 is highlyexpressed in endothelial venules (HEV) such as high endothelial venulesin lymphoid organs, as well as hepatic sinusoidal endothelial cells,(HSEC), smooth muscle cells, and adipocytes. The VAP-1 expression on thecell surface of endothelial cells is strictly regulated and is increasedduring inflammation. VAP-1 activates NF-κB when it is present in thesubstrate, and the NF-κB is activated within the HSEC while E-selectinand chemokine IL-8 that are other adhesion molecules are upregulated exvivo. This suggests that VAP-1 may be a key factor for the regulation ofthe inflammatory response. Therefore, it seems likely that VAP-1inhibitors may be effective anti-inflammatory drugs in a wide range ofhuman diseases.

Nonalcoholic fatty liver disease (NAFLD), histologically, encompassessimple steatosis, nonalcoholic hepatosteatosis (NASH), and livercirrhosis. Among these, unlike simple steatosis (non-alcoholic fattyliver, NAFL), NASH potentially progresses to liver cirrhosis andhepatoma (hepatocellular carcinoma). In NASH, insulin resistance isknown to play an important role in the progression of disease, alongwith oxidative stress, inflammatory cascade, and fibrosis. In patientswith NAFLD, sVAP-1 levels were found to be elevated, and in VAP-1knockout (K/O) mice, carbon tetrachloride-induced liver fibrosis wasreduced compared with that in wild type animals. In addition,improvement of liver fibrosis by VAP-1 inhibition followingadministration of VAP-1 antibody was identified by histological changes[J Clin Invest (2015) 125: 501]. Thus, VAP-1 was found to be associatedwith NASH in clinical studies and animal models of diseases. Inhibitoryactivity of VAP-1 in the carbon tetrachloride-induced animal modelappears to be due to a reduction in infiltration of leukocytes such as Tcells, B cells, NKT cells, and NK cells observed in liver fibrosis, andVAP-1 inhibitors have the potential for treating fibrotic diseases.

Thus, a substance that inhibits VAP-1 may be applied to prevention andtreatment of various inflammatory diseases and fibrotic diseases.

SUMMARY

The present inventors found that triazolones having3,3-difluoroallylamine groups or their pharmaceutically acceptable saltsexhibit inhibitory activity on VAP-1. Therefore, the3,3-difluoroallylamines or their salts can be usefully used in thetreatment and prophylaxis of various VAP-1 mediated diseases, forexample, nonalcoholic hepatosteatosis (NASH).

Therefore, the present technology provides the 3,3-difluoroallylaminesor their pharmaceutically acceptable salts, preparation processesthereof, pharmaceutical compositions comprising the same, and the usethereof.

In accordance with one aspect of the present technology, there isprovided a 3,3-difluoroallylamine or its pharmaceutically acceptablesalt.

In accordance with another aspect of the present technology, there isprovided a preparation process of the 3,3-difluoroallylamine or itspharmaceutically acceptable salt.

In accordance with another aspect of the present technology, there isprovided a pharmaceutical composition comprising the3,3-difluoroallylamine or its pharmaceutically acceptable salt as anactive ingredient.

In accordance with another aspect of the present technology, there isprovided a method of treatment comprising administering the3,3-difluoroallylamine or its pharmaceutically acceptable salt.

In accordance with another aspect of the present technology, there isprovided the use of the 3,3-difluoroallylamine or its pharmaceuticallyacceptable salt in the manufacture of a medicament for inhibition ofvascular adhesion protein-1.

It was found by the present technology that triazolones having3,3-difluoroallylamine groups or their pharmaceutically acceptable saltsexhibit inhibitory activity on VAP-1. Therefore, the compounds accordingto the present technology or pharmaceutically acceptable salts thereofcan be usefully applied for the treatment and prophylaxis of VAP-1mediated various diseases, for example, nonalcoholic hepatosteatosis(NASH).

Provided herein in one aspect is a compound of Formula X

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

n is 0, 1 or 2; and

A is an aryl group or a heterocyclic group, wherein said heterocyclicgroup has 1 to 5 heteroatom ring members chosen from O, N, or S, andsaid heterocyclic group is aromatic or non-aromatic; and wherein saidaryl group or said heterocyclic group is optionally substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R; and

R is a substituted or unsubstituted cyclic ring, optionally containing 1to 5 heteroatom ring members chosen from O, N, or S, and said cyclicring is aromatic or non-aromatic. In some embodiments, A is aryloptionally substituted with one or two substituents selected from thegroup consisting of C₁₋₃ alkyl, halogen, benzyloxy, —R, —CH═CH—R, and—C≡C—R. In some embodiments, A is phenyl substituted with one or twosubstituents selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C≡C—R. In some embodiments, A is aheterocyclic group having 1 to 5 heteroatom ring members chosen from O,N, or S; said heterocyclic group is aromatic or non-aromatic; and saidheterocyclic group is optionally substituted with one or twosubstituents selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C≡C—R. In some embodiments, A is aheteroaryl group having 1 to 5 heteroatom ring members chosen from O, N,or S; and said heteroaryl group is optionally substituted with one ortwo substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R. In some embodiments, A ispyridine, pyrazine, or thiophene, wherein A is optionally substitutedwith one or two substituents selected from the group consisting of C₁₋₃alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R. In someembodiments, R is a cyclic ring optionally containing 1-5 heteroatomring members, and said cyclic ring is optionally substituted with one tothree substituents selected from the group consisting of halogen, C₁₋₆alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino,C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, pyrrolidinonyl,and pyrrolidinyl. In some embodiments, n is 0. In some embodiments, nis 1. In some embodiments, n is 2.

Provided herein in another aspect is a compound, of Formula Y

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

n is 0, 1 or 2;

A is an aryl or heteroaryl group selected from the group consisting ofphenyl, pyridine, pyrazine, thiophene, and benzothiophene;

wherein said aryl or heteroaryl group is optionally substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R;

wherein said R is a cyclic ring selected from the group consisting ofbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine,imidazole, pyrazole, benzodioxole, benzoxadiazole, benzothiazole,indazole, 1,3-dihydroindol-2-one, quinolin-2-one,3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,3,4-dihydro-1,4-benzoxazine, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene;

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, pyrrolidinonyl,and pyrrolidinyl.

In some embodiments, n is 0 or 1, and A is phenyl, pyridine orthiophene, optionally substituted with one or two substituents selectedfrom the group consisting of C₁₋₃ alkyl, halogen, benzyloxy, —R,—CH═CH—R, and —C≡C—R. In some embodiments, said aryl or heteroaryl groupis substituted with one or two substituents selected from the groupconsisting of C₁₋₃ alkyl, halogen, and —R. In some embodiments, said Ris a cyclic ring selected from the group consisting of benzene,pyridine, pyridin-2-one, pyrazole and 3,4-dihydroquinolin-2-one, saidcyclic ring is optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl,acetylpiperazinyl, morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.In some embodiments, said cyclic ring is substituted with a substituentselected from the group consisting of C₁₋₆ alkyl, C₁₋₆ alkylsulfonyl,di-C₁₋₆ alkylamino, and piperazinyl. In some embodiments, n is 0; A isphenyl; wherein said phenyl is substituted with one or two substituentsselected from the group consisting of halogen and —R; wherein said R isa cyclic ring selected from the group consisting of benzene, pyridine,3,4-dihydroquinolin-2-one and pyrazole; and wherein said cyclic ring issubstituted with a substituent selected from the group consisting ofC₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆ alkylamino, and piperazinyl. Insome embodiments, n is 0; A is pyridine; wherein said pyridine issubstituted with one or two substituents selected from the groupconsisting of C₁₋₃ alkyl, halogen, and —R; wherein said R is a cyclicring selected from the group consisting of benzene, pyridine,3,4-dihydroquinolin-2-one and pyrazole; and wherein said cyclic ring issubstituted with a substituent selected from the group consisting ofC₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆ alkylamino, and piperazinyl. Insome embodiments, n is 0; A is thiophene; wherein said thiophene issubstituted with one or two cyclic rings selected from the groupconsisting of benzene, pyridine, pyridin-2-one,3,4-dihydroquinolin-2-one and pyrazole; and wherein said cyclic ring issubstituted with a substituent selected from the group consisting ofC₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆ alkylamino, and piperazinyl. Insome embodiments, A is phenyl optionally substituted with one or twosubstituents selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C≡C—R. In some embodiments, A is phenylsubstituted with —R. In some embodiments, —R is a cyclic ring selectedfrom the group consisting of benzene, pyridine, pyridin-2-one, pyrazole,benzodioxole, and 3,4-dihydroquinolin-2-one; wherein said cyclic ring isoptionally substituted with one to three substituents selected from thegroup consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinonyl. In someembodiments, A is pyridine substituted with —R. In some embodiments, —Ris a cyclic ring selected from the group consisting of benzene,pyridine, pyridin-2-one, pyrimidine, pyrazole, benzodioxole,benzoxadiazole, benzothiazole, indazole, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,1,4-dihydroquinazolin-2-one, 1H-pyrrolo[2,3-b]pyridine, benzoxazole, andthiophene. wherein said cyclic ring is optionally substituted with oneto three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono-C₁₋₆ alkylaminocarbonyl, mono-or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl,C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinonyl. In someembodiments, A is thiophene substituted with —R. In some embodiments, —Ris a cyclic ring selected from the group consisting of benzene,pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, imidazole,pyrazole, benzodioxole, benzoxadiazole, benzothiazole, indazole,1,3-dihydroindol-2-one, quinolin-2-one, 3,4-dihydroisoquinolin-1-one,3,4-dihydroquinolin-2-one, 2,3-dihydro-1,4-benzoxazine,1,4-dihydro-3,1-benzoxazin-2-one, 5,6,7,8-tetrahydronaphthyridine,triazolo[1,5-a]pyridine, pyrido[2,3-b][1,4]oxazin-2-one, and1,4-dihydroquinazolin-2-one; wherein said cyclic ring is optionallysubstituted with one to three substituents selected from the groupconsisting of halogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl,(cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl. In some embodiments, A isbenzothiophene substituted with —R. In some embodiments, —R is a cyclicring selected from the group consisting of benzene, pyridine,pyridin-2-one, pyrazole, benzodioxole, and 3,4-dihydroquinolin-2-one,wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl. In someembodiments, n is 0. In some embodiments, n is 1. In some embodiments, nis 2.

Provided herein in another aspect is a compound of Formula 12

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl group or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is halogen.In some embodiments, R¹ is C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted aryl group. In some embodiments, R² issubstituted or unsubstituted phenyl. In some embodiments, R² is phenylsubstituted with triazolyl, C₁₋₆ alkylsulfonyl, or piperazinyl. In someembodiments, R² is benzodioxole or 3,4-dihydroquinolin-2-one, whereinsaid 3,4-dihydroquinolin-2-one is optionally substituted with C₁₋₆alkyl. In some embodiments, R² is a substituted or unsubstitutedheteroaryl group, wherein said heteroaryl group has 1 to 5 heteroatomring members chosen from O, N, or S. In some embodiments, R² issubstituted or unsubstituted pyridine. In some embodiments, R² ispyridine substituted with trifluoromethyl or mono- or di-C₁₋₆alkylamino. In some embodiments, R² is substituted or unsubstitutedpyrazole. In some embodiments, R² is pyrazole substituted with C₁₋₆alkyl or difluoromethyl.

Provided herein in another aspect is a compound of Formula 13

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aralkoxy group, a substituted orunsubstituted aryl group, or a substituted or unsubstituted heterocyclicgroup, wherein said heterocyclic group has 1 to 5 heteroatom ringmembers chosen from O, N, or S, and said heterocyclic group is aromaticor non-aromatic.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is halogen.In some embodiments, R¹ is C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted aryl group. In some embodiments, R² issubstituted or unsubstituted phenyl. In some embodiments, R² is phenylsubstituted with C₁₋₆ alkylsulfonyl or piperazinyl. In some embodiments,R² is benzodioxole or 3,4-dihydroquinolin-2-one, wherein said3,4-dihydroquinolin-2-one is optionally substituted with C₁₋₆ alkyl. Insome embodiments, R² is a substituted or unsubstituted heteroaryl group,wherein said heteroaryl group has 1 to 5 heteroatom ring members chosenfrom O, N, or S. In some embodiments, R² is substituted or unsubstitutedpyridine. In some embodiments, R² is pyridine substituted with mono- ordi-C₁₋₆ alkylamino. In some embodiments, R² is substituted orunsubstituted pyrazole. In some embodiments, R² is pyrazole substitutedwith C₁₋₆ alkyl. In some embodiments, R² is substituted or unsubstitutedpyridin-2-one. In some embodiments, R² is pyridin-2-one substituted withC₁₋₆ alkyl. In some embodiments, R² is substituted or unsubstitutedaralkoxy group. In some embodiments, R² is substituted or unsubstitutedbenzyloxy.

Provided herein in another aspect is a compound of Formula 14

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

In some embodiments, the compound is of Formula 14a

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.In some embodiments, the compound is of Formula 14b

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.In some embodiments, the compound is of Formula 14c

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is halogen.In some embodiments, R¹ is C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted aryl group. In some embodiments, R² issubstituted or unsubstituted phenyl. In some embodiments, R² is phenylsubstituted with one to three substituents selected from the groupconsisting of with halogen, C₁₋₆ alkoxy, mono- or di-C₁₋₆ alkylamino,mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl,morpholinylcarbonyl, piperazinyl, morpholinyl, pyrazolyl, C₁₋₆alkylpyrazolyl, triazolyl, and pyrrolidinonyl. In some embodiments, R²is benzodioxole, benzoxadiazole, benzothiazole, indazole,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 1,4-dihydroquinazolin-2-one,3,4-dihydroquinolin-2-one, or benzoxazole, wherein R² is optionallysubstituted with C₁₋₆ alkyl or amino. In some embodiments, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. In someembodiments, R² is substituted or unsubstituted pyridine. In someembodiments, R² is pyridine substituted with C₁₋₆ alkoxy,trifluoromethyl, piperazinyl, morpholinyl, or mono- or di-C₁₋₆alkylamino. In some embodiments, R² is pyrimidine,1H-pyrrolo[2,3-b]pyridine, pyrazole, or thiophene, wherein R² isoptionally substituted with C₁₋₆ alkyl, difluoromethyl, C₁₋₆ alkoxy-C₁₋₆alkylamino, or C₁₋₆ alkylcarbonyl. In some embodiments, R² issubstituted or unsubstituted pyridin-2-one. In some embodiments, R² ispyridin-2-one substituted with C₁₋₆ alkyl.

Provided herein in another aspect is a compound of Formula 15

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S group.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is C₁₋₆alkyl. In some embodiments, R² is a substituted or unsubstituted arylgroup. In some embodiments, R² is substituted or unsubstituted phenyl.In some embodiments, R² is 2,3-dihydro-1,4-benzoxazine or3,4-dihydroquinolin-2-one, wherein said 3,4-dihydroquinolin-2-one isoptionally substituted with C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. In someembodiments, R² is substituted or unsubstituted pyridine. In someembodiments, R² is pyridine substituted with morpholinyl or mono- ordi-C₁₋₆ alkylamino. In some embodiments, R² is2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, or pyrazole, wherein said pyrazole isoptionally substituted with C₁₋₆ alkyl.

Provided herein in another aspect is a compound of Formula 16

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments, R² is a substituted or unsubstituted aryl group. Insome embodiments, R² is substituted or unsubstituted phenyl. In someembodiments, R² is phenyl substituted with C₁₋₆ alkylsulfonyl orpiperazinyl. In some embodiments, R² is benzodioxole or3,4-dihydroquinolin-2-one, wherein said 3,4-dihydroquinolin-2-one isoptionally substituted with C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. In someembodiments, R² is substituted or unsubstituted pyridine. In someembodiments, R² is pyridine substituted with trifluoromethyl or mono- ordi-C₁₋₆ alkylamino. In some embodiments, R² is substituted orunsubstituted pyrazole. In some embodiments, R² is pyrazole substitutedwith C₁₋₆ alkyl.

Provided herein in another aspect is a compound of Formula 17

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is halogen.In some embodiments, R¹ is C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted aryl group. In some embodiments, R² issubstituted or unsubstituted phenyl. In some embodiments, R² is phenylsubstituted with one to three substituents selected from the groupconsisting of C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkylsulfonyl, mono-or di-C₁₋₆ alkylaminosulfonyl, mono- or di-C₁₋₆ alkylaminocarbonyl,morpholinylcarbonyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl,piperazinyl, and acetylpiperazinyl. In some embodiments, R² is3,4-dihydroisoquinolin-1-one, quinolin-2-one,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 1,4-dihydroquinazolin-2-one,benzothiazole, benzoxadiazole, indazole, benzodioxole,1,3-dihydroindol-2-one, or 3,4-dihydroquinolin-2-one; wherein R² isoptionally substituted with C₁₋₆ alkyl, C₁₋₆ alkylcarbonylamino, orhalogen. In some embodiments, R² is a substituted or unsubstitutedheteroaryl group, wherein said heteroaryl group has 1 to 5 heteroatomring members chosen from O, N, or S. In some embodiments, R² issubstituted or unsubstituted pyridine. In some embodiments, R² ispyridine substituted with one to three substituents selected from thegroup consisting of halogen, trifluoromethyl, C₁₋₆ alkoxy, piperazinyland mono- or di-C₁₋₆ alkylamino. In some embodiments, R² is substitutedor unsubstituted pyrazole. In some embodiments, R² is pyrazolesubstituted with C₁₋₆ alkyl, difluoromethyl, benzyl, (cycloalkyl)alkyl,alkylsulfonyl, or cycloalkylsulfonyl. In some embodiments, R² is5,6,7,8-tetrahydronaphthyridine, pyrimidine, imidazole, ortriazolo[1,5-a]pyridine; wherein R² is optionally substituted with oneto three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, C₁₋₆ alkoxy, amino, and C₁₋₆ alkoxy-C₁₋₆ alkylamino. In someembodiments, R² is [1,2,4]triazolo[1,5-a]pyridine. In some embodiments,R² is tetrahydropyridine or pyridin-2-one, wherein saidtetrahydropyridine and said pyridin-2-one are optionally substitutedwith C₁₋₆ alkyl or C₁₋₆ alkylcarbonyl.

Provided herein in another aspect is a compound of Formula 18

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is halogen.In some embodiments, R¹ is C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted aryl group. In some embodiments, R² issubstituted or unsubstituted phenyl. In some embodiments, R² is2,3-dihydro-1,4-benzoxazine or 3,4-dihydroquinolin-2-one. In someembodiments, R² is a substituted or unsubstituted heteroaryl group,wherein said heteroaryl group has 1 to 5 heteroatom ring members chosenfrom O, N, or S. In some embodiments, R² is substituted or unsubstitutedpyridine. In some embodiments, R² is pyridine substituted withmorpholinyl or mono- or di-C₁₋₆ alkylamino. In some embodiments, R² issubstituted or unsubstituted pyrazole. In some embodiments, R² ispyrazole substituted with C₁₋₆ alkyl. In some embodiments, R² is2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,or pyrido[3,2-b][1,4]oxazin-3-one.

Provided herein in another aspect is a compound of Formula 19

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is halogen.In some embodiments, R¹ is C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted aryl group. In some embodiments, R² issubstituted or unsubstituted phenyl. In some embodiments, R² is phenylsubstituted with C₁₋₆ alkylsulfonyl or piperazinyl. In some embodiments,R² is benzodioxole or 3,4-dihydroquinolin-2-one; wherein R² isoptionally substituted with C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. In someembodiments, R² is substituted or unsubstituted pyridine. In someembodiments, R² is pyridine substituted with trifluoromethyl or mono- ordi-C₁₋₆ alkylamino. In some embodiments, R² is substituted orunsubstituted pyrazole. In some embodiments, R² is pyrazole substitutedwith C₁₋₆ alkyl.

Provided herein in another aspect is a compound of Formula 20

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is halogen.In some embodiments, R¹ is C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted aryl group. In some embodiments, R² issubstituted or unsubstituted phenyl. In some embodiments, R² is phenylsubstituted with C₁₋₆ alkylsulfonyl or piperazinyl. In some embodiments,R² is benzodioxole or 3,4-dihydroquinolin-2-one; wherein R² isoptionally substituted with C₁₋₆ alkyl. In some embodiments, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. In someembodiments, R² is substituted or unsubstituted pyridine. In someembodiments, R² is pyridine substituted with trifluoromethyl or mono- ordi-C₁₋₆ alkylamino. In some embodiments, R² is substituted orunsubstituted pyrazole. In some embodiments, R² is pyrazole substitutedwith C₁₋₆ alkyl. In some embodiments, R² is a substituted orunsubstituted pyridine-2-one. In some embodiments, R² is pyridine-2-onesubstituted with C₁₋₆ alkyl. In some embodiments, the compound, or astereoisomer thereof or a pharmaceutically acceptable salt thereof, isselected from Table 1.

Provided herein in another aspect is a pharmaceutical compositioncomprising the compound disclosed herein, or a stereoisomer thereof, ora pharmaceutically acceptable salt thereof, and at least onepharmaceutically acceptable excipient

Provided herein in another aspect is a method of inhibiting vascularadhesion protein (VAP-1), comprising administering to a mammal, atherapeutically effective amount of the compound disclosed herein, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof.

Provided herein in another aspect is a method of treating NASH in asubject in need thereof, the method comprising administering to thesubject a therapeutically effective amount of the compound disclosedherein, or a stereoisomer thereof, or a pharmaceutically acceptable saltthereof, or a therapeutically effective amount of the pharmaceuticalcomposition disclosed herein.

Provided herein in another aspect is a use of the compound disclosedherein, or a stereoisomer thereof, or a pharmaceutically acceptable saltthereof, for the manufacture of a medicament for the treatment of NASH.

Provided herein in another aspect is a compound disclosed herein, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse in treating NASH.

Provided herein in another aspect is a composition disclosed herein foruse in treating NASH.

Provided herein in another aspect is a compound disclosed herein, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse in inhibiting VAP-1.

Provided herein in another aspect is a composition disclosed herein foruse in inhibiting VAP-1.

Provided herein in another aspect is a method of treating a diseasemediated by VAP-1 in a subject in need thereof, the method comprisingadministering to the subject a therapeutically effective amount of thecompound disclosed herein, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof, or a therapeutically effectiveamount of the pharmaceutical composition disclosed herein. In someembodiments, the disease mediated by VAP-1 is selected from the groupconsisting of lipid and lipoprotein disorders, conditions and diseaseswhich result from chronic fatty and fibrotic degeneration of organs dueto accumulated lipid and specifically triglyceride accumulation andsubsequent activation of profibrotic pathways, Type I or Type IIDiabetes and clinical complications of Type I and Type II Diabetes,chronic intrahepatic or some forms of extrahepatic cholestaticconditions, liver fibrosis, acute intraheptic cholestatic conditions,obstructive or chronic inflammatory disorders that arise out of improperbile composition, gastrointestinal conditions with a reduced uptake ofdietary fat and fat-soluble dietary vitamins, inflammatory boweldiseases, obesity and metabolic syndrome (combined conditions ofdyslipidemia, diabetes and abnormally high body-mass index), persistentinfections by intracellular bacteria or parasitic protozoae,non-malignant hyperproliferative disorders, malignant hyperproliferativedisorders, colon adenocarcinoma and hepatocellular carcinoma inparticular, liver steatosis and associated syndromes, Hepatitis Binfection, Hepatitis C infection and/or of cholestatic and fibroticeffects that are associated with alcohol-induced cirrhosis or withviral-borne forms of hepatitis, liver failure or liver malfunction as anoutcome of chronic liver diseases or of surgical liver resection, acutemyocardial infarction, acute stroke, thrombosis which occurs as anendpoint of chronic obstructive atherosclerosis, osteoarthritis,rheumatoid arthritis, psoriasis, and cerebral infarction, individuallyor any combination thereof.

Provided herein in another aspect is a method of preparing a compound ofFormula 1aa, or a stereoisomer thereof, or a pharmaceutically acceptablesalt thereof,

the method comprising

(a) reacting a compound of Formula 2 with a compound of Formula 3a or acompound of Formula 3b to obtain a compound of Formula 1a

wherein

Boc is an amine protecting group;

n is 0, 1, or 2;

A′ is aryl or heteroaryl group selected from the group consisting ofphenyl, pyridine, pyrazine, thiophene, and benzothiophene; wherein saidaryl or heteroaryl group is optionally substituted with C₁₋₃ alkyl orhalogen;

Z is boronic acid (B(OH)₂) or boronic acid pinacol ester;

R′ is —R, —CH═CH—R, or —C≡C—R; and

R is a substituted or unsubstituted cyclic ring, optionally containing 1to 5 heteroatom ring members chosen from O, N, or S, and said cyclicring is aromatic or non-aromatic; and

(b) removing Boc from the compound of Formula 1a under reactionconditions to obtain the compound of Formula 1aa, or the stereoisomerthereof, or the pharmaceutically acceptable salt thereof.

In some embodiments, the cyclic ring is selected from the groupconsisting of benzene, pyridine, tetrahydropyridine, pyridin-2-one,pyrimidine, imidazole, pyrazole, benzodioxole, benzoxadiazole,benzothiazole, indazole, 1,3-dihydroindol-2-one, quinolin-2-one,3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,3,4-dihydro-1,4-benzoxazine, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene;

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl,acetylpiperazinyl, morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

DETAILED DESCRIPTION

It is noted that, as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. It is further noted that the claimsmay be drafted to exclude any optional element. As such, this statementis intended to serve as antecedent basis for use of such exclusiveterminology as “solely”, “only” and the like in connection with therecitation of claim elements, or use of a “negative” limitation.

As used herein, the term “comprising” or “comprises” is intended to meanthat the compositions and methods include the recited elements, but notexcluding others. A composition or method “consisting essentially” ofthe elements as defined herein would not exclude other materials orsteps that do not materially affect the basic and novelcharacteristic(s) of the claimed technology. “Consisting of” shall meanexcluding more than trace elements of other ingredients and substantialmethod steps. Embodiments defined by each of these transition terms arewithin the scope of this technology. When an embodiment is defined byone of these terms (e.g., “comprising”) it should be understood thatthis disclosure also includes alternative embodiments, such as“consisting essentially of” and “consisting of” for said embodiment.

“Substantially” or “essentially” means nearly totally or completely, forinstance, 95%, 96%, 97%, 98%, 99%, or greater of some given quantity.

As used herein, the term “about” will be understood by persons ofordinary skill in the art and will vary to some extent depending uponthe context in which it is used. If there are uses of the term which arenot clear to persons of ordinary skill in the art given the context inwhich it is used, “about” will mean up to plus or minus 10% of theparticular term.

Certain ranges are presented herein with numerical values being precededby the term “about”. The term “about” is used herein to provide literalsupport for the exact number that it precedes, as well as a number thatis near to or approximately the number that the term precedes. Indetermining whether a number is near to or approximately a specificallyrecited number, the near or approximating unrecited number may be anumber which, in the context in which it is presented, provides thesubstantial equivalent of the specifically recited number.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the present technology. The upperand lower limits of these smaller ranges may independently be includedin the smaller ranges and are also encompassed within the presenttechnology, subject to any specifically excluded limit in the statedrange. Where the stated range includes one or both of the limits, rangesexcluding either or both of those included limits are also included inthe present technology.

In general, “substituted” refers to an organic group (e.g., an alkylgroup) in which one or more bonds to a hydrogen atom contained thereinare replaced by a bond to non-hydrogen or non-carbon atoms. Substitutedgroups also include groups in which one or more bonds to a carbon(s) orhydrogen(s) atom are replaced by one or more bonds, including double ortriple bonds, to a heteroatom. The present disclosure is understood toinclude embodiments where, for instance a “substituted alkyl” optionallycontains one or more alkene and/or alkyne. A substituted group will besubstituted with one or more substituents, unless otherwise specified.In some embodiments, a substituted group is substituted with 1, 2, 3, 4,5, or 6 substituents. Examples of substituent groups include: alkylgroups; haloalkyl groups; halogens (i.e., F, Cl, Br, and I); hydroxyls;alkoxy, alkenoxy, alkynoxy, aryloxy, aralkyloxy, heterocyclyloxy, andheterocyclylalkoxy groups; aryl groups; heteroaryl groups; cycloalkylgroups; heterocyclyl groups; carbonyls (oxo); carboxyls; esters;carbamates; urethanes; ureas; oximes; hydroxylamines; alkoxyamines;aralkoxyamines; thiols; sulfides; sulfoxides; sulfones; sulfonyls;sulfonamides; amines; N-oxides; hydrazines; hydrazides; hydrazones;azides; amides; ureas; amidines; guanidines; enamines; imides;isocyanates; isothiocyanates; cyanates; thiocyanates; imines; nitrogroups; nitriles (i.e., CN); and the like. The substituent may be asubstituted or unsubstituted cyclic ring. As used herein, an “optionallysubstituted” group refers to substituted or unsubstituted group.Accordingly, “optionally substituted” and “substituted or unsubstituted”may be used interchangeably.

Substituted ring groups such as substituted cyclic, substitutedcycloalkyl, substituted aryl, substituted heterocyclic and substitutedheteroaryl groups also include rings and fused ring systems in which abond to a hydrogen atom is replaced with a bond to a carbon atom.Therefore, substituted cyclic, substituted cycloalkyl, substituted aryl,substituted heterocyclic and substituted heteroaryl groups may also besubstituted with substituted or unsubstituted alkyl, alkenyl, andalkynyl groups as defined below.

As used herein, the term “cyclic ring” refers to an aromatic ornon-aromatic ring, optionally containing one or more heteroatoms.Exemplary heteroatoms include, but are not limited to, N, O, S, or B. Insome embodiments, the cyclic ring optionally contains 1 to 5 heteroatomring members chosen from O, N, or S. In some embodiments, the cyclicring optionally contains 1 to 4 heteroatom ring members chosen from O,N, or S. In some embodiments, the cyclic ring optionally contains 1 to 3heteroatom ring members chosen from O, N, or S. Cyclic rings includearyl, cycloalkyl, and heterocyclic groups. In some embodiments, thecyclic ring is selected from the group consisting of benzene, pyridine,tetrahydropyridine, pyridin-2-one, pyrimidine, imidazole, pyrazole,benzodioxole, benzoxadiazole, benzothiazole, indazole,1,3-dihydroindol-2-one, quinolin-2-one, 3,4-dihydroisoquinolin-1-one,3,4-dihydroquinolin-2-one, 3,4-dihydro-1,4-benzoxazine,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 5,6,7,8-tetrahydronaphthyridine,triazolo[1,5-a]pyridine, 2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene. As used herein,triazolo[1,5-a]pyridine includes [1,2,4]triazolo[1,5-a]pyridine and[1,2,3]triazolo[1,5-a]pyridine.

As used herein, an “aryl group” refers to a cyclic aromatic hydrocarbonthat does not contain heteroatoms. Aryl groups include monocyclic,bicyclic and polycyclic ring systems. Thus, aryl groups include, but arenot limited to, phenyl, azulenyl, heptalenyl, biphenylenyl, indacenyl,fluorenyl, phenanthrenyl, triphenylenyl, pyrenyl, naphthacenyl,chrysenyl, biphenyl, anthracenyl, indenyl, indanyl, pentalenyl, andnaphthyl groups. In some embodiments, aryl groups contain 6-14 carbons,and in others from 6 to 12 or even 6-10 carbon atoms in the ringportions of the groups. Although the phrase “aryl groups” includesgroups containing fused rings, such as fused aromatic-aliphatic ringsystems (e.g., benzodioxole, indanyl, tetrahydronaphthyl, and the like),it does not include aryl groups that have other groups, such as alkyl orhalo groups, bonded to one of the ring members. Rather, groups such astolyl are referred to as substituted aryl groups. Representativesubstituted aryl groups may be mono-substituted or substituted more thanonce. For example, monosubstituted aryl groups include, but are notlimited to, 2-, 3-, 4-, 5-, or 6-substituted phenyl or naphthyl groups,which may be substituted with substituents such as those listed above.

As used herein, the term “cycloalkyl group” refers to a cyclic alkylgroup such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, and cyclooctyl groups. In some embodiments, thecycloalkyl group has 3 to 8 carbon ring members, whereas in otherembodiments the number of ring carbon atoms range from 3 to 5, 3 to 6,or 3 to 7. Cycloalkyl groups further include mono-, bicyclic andpolycyclic ring systems, such as, for example bridged cycloalkyl groupsas described below, and fused rings, such as, but not limited to,decalinyl, and the like. In some embodiments, polycyclic cycloalkylgroups have three rings. Substituted cycloalkyl groups may besubstituted one or more times with non-hydrogen and non-carbon groups asdefined above. However, substituted cycloalkyl groups also include ringsthat are substituted with straight or branched chain alkyl groups asdefined above. Representative substituted cycloalkyl groups may bemono-substituted or substituted more than once, such as, but not limitedto, 2,2-, 2,3-, 2,4-2,5- or 2,6-di-substituted cyclohexyl groups, whichmay be substituted with substituents such as those listed above. In someembodiments, a cycloalkyl group has one or more alkene bonds, but is notaromatic. As used herein, the term “(cycloalkyl)alkyl” refers to analkyl group substituted with a cycloalkyl group.

As used herein, the term “heterocyclic” or “heterocyclyl” includesaromatic (also referred to as heteroaryl) and non-aromatic ringcompounds containing 3 or more ring members, of which one or more is aheteroatom such as, but not limited to, N, O, S or B. In someembodiments, heterocyclic groups include 3 to 20 ring members, whereasother such groups have 3 to 6, 3 to 10, 3 to 12, or 3 to 15 ringmembers. The heterocyclic group may have 1 to 5 heteroatom ring memberschosen from O, N, or S. Heterocyclic groups encompass unsaturated,partially saturated and saturated ring systems, such as, for example,imidazolyl, imidazolinyl and imidazolidinyl groups. The phrase“heterocyclic group” includes fused ring species including thosecomprising fused aromatic and non-aromatic groups, such as, for example,benzotriazolyl, 2,3-dihydrobenzo[1,4]dioxinyl, and benzo[1,3]dioxolyl.The phrase also includes bridged polycyclic ring systems containing aheteroatom such as, but not limited to, quinuclidyl. However, the phrasedoes not include heterocyclic groups that have other groups, such asalkyl, oxo or halo groups, bonded to one of the ring members. Rather,these are referred to as “substituted heterocyclic groups”. Heterocyclicgroups include, but are not limited to, aziridinyl, azetidinyl,pyrrolidinyl, imidazolidinyl, pyrazolidinyl, thiazolidinyl,tetrahydrothiophenyl, tetrahydrofuranyl, dioxolyl, furanyl, thiophenyl,pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl,triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiazolinyl,isothiazolyl, thiadiazolyl, oxadiazolyl, piperidyl, piperazinyl,morpholinyl, thiomorpholinyl, tetrahydropyranyl, tetrahydrothiopyranyl,oxathiane, dioxyl, dithianyl, pyranyl, pyridyl, pyrimidinyl,pyridazinyl, pyrazinyl, triazinyl, dihydropyridyl, dihydrodithiinyl,dihydrodithionyl, homopiperazinyl, quinuclidyl, indolyl, indolinyl,isoindolyl, azaindolyl (pyrrolopyridyl), indazolyl, indolizinyl,benzotriazolyl, benzimidazolyl, benzofuranyl, benzothiophenyl,benzthiazolyl, benzoxadiazolyl, benzoxazinyl, benzodithiinyl,benzoxathiinyl, benzothiazinyl, benzoxazolyl, benzothiazolyl,benzothiadiazolyl, benzo[1,3]dioxolyl, pyrazolopyridyl, imidazopyridyl(azabenzimidazolyl), triazolopyridyl, isoxazolopyridyl, purinyl,xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, quinolizinyl,quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl,pteridinyl, thianaphthalenyl, dihydrobenzothiazinyl,dihydrobenzofuranyl, dihydroindolyl, dihydrobenzodioxinyl,tetrahydroindolyl, tetrahydroindazolyl, tetrahydrobenzimidazolyl,tetrahydrobenzotriazolyl, tetrahydropyrrolopyridyl,tetrahydropyrazolopyridyl, tetrahydroimidazopyridyl,tetrahydrotriazolopyridyl, and tetrahydroquinolinyl groups.Representative substituted heterocyclic groups may be mono-substitutedor substituted more than once, such as, but not limited to, pyridyl orpiperazinyl groups, which are 2-, 3-, 4-, 5-, or 6-substituted, ordisubstituted with various substituents such as those listed above.

As used herein, the term “heteroaryl group” refers to an aromatic ringcompound containing 5 or more ring members, of which, one or more is aheteroatom such as, but not limited to, N, O, S or B. In someembodiments, one or more heteroatoms are chosen from N, O, or S. In someembodiments, 1 to 4 heteroatoms are chosen from N, O, or S. In someembodiments, 1 to 5 heteroatoms are chosen from N, O, or S. In someembodiments, heteroaryl groups include 5 to 14 ring members, whereasother such groups have 5 to 6, 5 to 9, 5 to 10, 6 to 9, 6 to 10, or 6 to14 ring members. For example, a 5-membered heteroaryl group has 5 ringmembers; a 6-membered heteroaryl group has 6 ring members; and a9-membered heteroaryl group has 9 ring members (such as, but not limitedto, benzothiophene). Heteroaryl groups include, but are not limited to,groups such as pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl,isoxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,thiophenyl, benzothiophenyl, furanyl, benzofuranyl, indolyl, azaindolyl(pyrrolopyridyl), indazolyl, benzimidazolyl, imidazopyridyl(azabenzimidazolyl), pyrazolopyridyl, triazolopyridyl, benzotriazolyl,benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridyl,isoxazolopyridyl, thianaphthalenyl, purinyl, xanthinyl, adeninyl,guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl,and quinazolinyl groups. Although the phrase “heteroaryl groups”includes fused ring compounds such as indolyl and 2,3-dihydro indolyl,the phrase does not include heteroaryl groups that have other groupsbonded to one of the ring members, such as alkyl groups. Rather,heteroaryl groups with such substitution are referred to as “substitutedheteroaryl groups.” Representative substituted heteroaryl groups may besubstituted one or more times with various substituents such as thoselisted above. An azolyl group is a 5-membered heteroaryl groupcontaining a nitrogen atom and at least one other atom selected fromnitrogen, sulfur, and oxygen as part of the ring. Azolyl groups includeimidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole,pentazole, oxazole, isoxazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole,1,3,4-oxadiazole, thiazole, isothiazole, 1,2,3-thiadiazole,1,2,4-thiadiazole, 1,2,5-thiadiazole, and 1,3,4-thiadiazole.

As used herein, the term “alkyl” refers to an aliphatic hydrocarbonradical, which encompasses both straight and branched hydrocarbonradicals. In some embodiments, alkyl has from 1 to about 20 carbonatoms, from 1 to 12 carbons, from 1 to 8 carbons, 1 to 6 carbons, or 1to 4 carbon atoms. For example, C₁₋₆ alkyl refers to an aliphatichydrocarbon having 1 to 6 carbons, which includes methyl, ethyl, propyl,n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl,neopentyl, isopentyl, and the like.

As used herein, the term “hydroxy” is defined as —OH.

As used herein, the term “alkoxy,” unless particularly defined herein,refers to a radical formed by substituting the hydrogen atom of ahydroxyl group with an alkyl. For example, C₁₋₆ alkoxy includes methoxy,ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy,tert-butoxy, neopentyloxy, isopentyloxy, and the like. An aralkoxy groupis an alkoxy group substituted with an aryl group. One non-limitingexample of an aralkoxy group is a substituted or unsubstituted benzyloxygroup.

In addition, the term “halogen” refers to fluorine, bromine, chlorine,and iodine.

In addition, the term “amino” is defined as —NH₂, and the term“alkylamino” refers to a mono- or di-alkyl substituted amino. Forexample, C₁₋₆ alkylamino includes mono- or di-C₁₋₆ alkyl substitutedamino.

In addition, the term “alkylthio” is defined as —SR (wherein R isalkyl), and the term “cyano” is defined as —CN.

Those of skill in the art will appreciate that compounds of the presenttechnology may exhibit the phenomena of tautomerism, conformationalisomerism, geometric isomerism and/or optical isomerism. As the formuladrawings within the specification and claims can represent only one ofthe possible tautomeric, conformational isomeric, optical isomeric orgeometric isomeric forms, it should be understood that the presenttechnology encompasses any tautomeric, conformational isomeric, opticalisomeric and/or geometric isomeric forms of the compounds having one ormore of the utilities described herein, as well as mixtures of thesevarious different forms. As used herein, “isomer” refers to a tautomer,conformation isomer, optical isomer, geometric isomer, or anycombination thereof, of a compound. Structural isomers are not includedin the meaning of “isomer” as used herein.

As readily understood by one skilled in the art, a wide variety offunctional groups and other structures may exhibit tautomerism, and alltautomers of compounds as described herein are within the scope of thepresent technology.

Stereoisomers of compounds, also known as “optical isomers,” include allchiral, diastereomeric, and racemic forms of a structure, unless thespecific stereochemistry is expressly indicated. Thus, compounds used inthe present technology include enriched or resolved optical isomers atany or all stereogenic atoms as are apparent from the depictions. Bothracemic and diastereomeric mixtures, as well as the individual opticalisomers can be isolated or synthesized so as to be substantially free oftheir enantiomeric or diastereomeric partners, and these are all withinthe scope of the present technology.

By “pharmaceutically acceptable” is meant a material that is notbiologically or otherwise undesirable, e.g., the material may beincorporated into a pharmaceutical composition administered to a patientwithout causing any undesirable biological effects or interacting in adeleterious manner with any of the other components of the compositionin which it is contained. When the term “pharmaceutically acceptable” isused to refer to a pharmaceutical carrier or excipient, it is impliedthat the carrier or excipient has met the required standards oftoxicological and manufacturing testing or that it is included on theInactive Ingredient Guide prepared by the U.S. Food and Drugadministration.

Generally, reference to a certain moiety capable of being protected(such as hydroxy, amine, carbonyl, etc.) includes the protected groupsin some embodiments of the disclosure. For example, in some embodiments,an —OH moiety as included herein also includes —OP, where P is aprotecting group. Protecting groups, as referred to herein may beselected by one of ordinary skill in the art, and include the groups andstrategies set forth in the art, for example, those such as described inR. Larock, Comprehensive Organic Transformations, VCH Publishers (1989);T. W. Greene and P. G. M. Wuts, Greene's protective groups in organicsynthesis, John Wiley & Sons (2006); L. Fieser and M. Fieser, Fieser andFieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); andL. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, JohnWiley and Sons (1995), and subsequent editions thereof.

“Subject” refers to an animal, such as a mammal (including a human),that has been or will be the object of treatment, observation orexperiment. “Subject” and “patient” may be used interchangeably, unlessotherwise indicated. The methods described herein may be useful in humantherapy and/or veterinary applications. In some embodiments, the subjectis a mammal. In some embodiments, the subject is a human.

The terms “therapeutically effective amount” and “effective amount” areused interchangibly and refer to an amount of a compound that issufficient to effect treatment as defined below, when administered to apatient (e.g., a human) in need of such treatment in one or more doses.The therapeutically effective amount will vary depending upon thepatient, the disease being treated, the weight and/or age of thepatient, the severity of the disease, or the manner of administration asdetermined by a qualified prescriber or care giver.

The term “treatment” or “treating” means administering a compounddisclosed herein for the purpose of: (i) delaying the onset of adisease, that is, causing the clinical symptoms of the disease not todevelop or delaying the development thereof, (ii) inhibiting thedisease, that is, arresting the development of clinical symptoms; and/or(iii) relieving the disease, that is, causing the regression of clinicalsymptoms or the severity thereof.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this present technology belongs. Although any methodsand materials similar or equivalent to those described herein can alsobe used in the practice or testing of the present technology,representative illustrative methods and materials are described herein.

The present technology provides a compound having inhibitory activity onVAP-1 or its salt, that is, a compound of Formula X:

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

n is 0, 1 or 2; and

A is an aryl group or a heterocyclic group, wherein said heterocyclicgroup has 1 to 5 heteroatom ring members chosen from O, N, or S, andsaid heterocyclic group is aromatic or non-aromatic; and wherein saidaryl group or said heterocyclic group is optionally substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R; and

R is a substituted or unsubstituted cyclic ring, optionally containing 1to 5 heteroatom ring members chosen from O, N, or S, and said cyclicring is aromatic or non-aromatic.

In another aspect, provided herein is a compound of Formula Y:

or a stereoisomer thereof, or a pharmaceutically acceptable saltthereof,

wherein

n is 0, 1 or 2,

A is an aryl or heteroaryl group selected from the group consisting ofphenyl, pyridine, pyrazine, thiophene, and benzothiophene,

wherein said aryl or heteroaryl group is optionally substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R,

wherein said R is a cyclic ring selected from the group consisting ofbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine,imidazole, pyrazole, benzodioxole, benzoxadiazole, benzothiazole,indazole, 1,3-dihydroindol-2-one, quinolin-2-one,3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,3,4-dihydro-1,4-benzoxazine, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene,

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, pyrrolidinonyl,and pyrrolidinyl.

In some embodiments of a compound of Formula X or Y, or a stereoisomerthereof, or a pharmaceutically acceptable salt thereof, said cyclic ringis optionally substituted with one to three substituents selected fromthe group consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In another aspect, provided herein is a compound of Formula 1:

or a stereoisomer thereof, or a pharmaceutically acceptable saltthereof,

wherein

n is 0, 1 or 2,

A is an aryl or heteroaryl group selected from the group consisting ofphenyl, pyridine, pyrazine, and thiophene, wherein said aryl orheteroaryl group is optionally substituted with one or two substituentsselected from the group consisting of C₁₋₃ alkyl, halogen, benzyloxy,—R, —CH═CH—R, and —C≡C—R,

wherein said R is a cyclic ring selected from the group consisting ofbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine,imidazole, pyrazole, benzodioxole, benzoxadiazole, benzothiazole,indazole, 1,3-dihydroindol-2-one, quinolin-2-one,3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,3,4-dihydro-1,4-benzoxazine, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,and pyrido[3,2-b][1,4]oxazin-3-one,

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,trifluoromethyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl,acetylpiperazinyl, morpholinyl, and pyrazolyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ais aryl optionally substituted with one or two substituents selectedfrom the group consisting of C₁₋₃ alkyl, halogen, benzyloxy, —R,—CH═CH—R, and —C≡C—R. In some embodiments of a compound of Formulas X,Y, or 1, or a stereoisomer thereof, or a pharmaceutically acceptablesalt thereof, A is phenyl substituted with one or two substituentsselected from the group consisting of C₁₋₃ alkyl, halogen, benzyloxy,—R, —CH═CH—R, and —C≡C—R.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ais a heterocyclic group having 1 to 5 heteroatom ring members chosenfrom O, N, or S; said heterocyclic group is aromatic or non-aromatic;and said heterocyclic group is optionally substituted with one or twosubstituents selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C≡C—R.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ais a heteroaryl group having 1 to 5 heteroatom ring members chosen fromO, N, or S; and said heteroaryl group is optionally substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R. In some embodiments of acompound of Formulas X, Y, or 1, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof, A is pyridine, pyrazine, orthiophene, wherein A is optionally substituted with one or twosubstituents selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C═C—R.

In the compound of Formulas X, Y, or 1, or the stereoisomer thereof, orits pharmaceutically acceptable salt thereof according to the presenttechnology, n may preferably be 0 or 1. In some embodiments, n is 0. Insome embodiments, n is 1. In some embodiments, n is 2.

Further, in the compound of Formulas X, Y, or 1, or the stereoisomerthereof, or its pharmaceutically acceptable salt thereof according tothe present technology, A may preferably be phenyl, pyridine, orthiophene, each of which is optionally substituted as described above.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ais phenyl, optionally substituted with one or two substituents selectedfrom the group consisting of C₁₋₃ alkyl, halogen, benzyloxy, —R,—CH═CH—R, and —C≡C—R. In further embodiments, A is phenyl substitutedwith —R. In some embodiments, A is phenyl substituted with —CH═CH—R or—C≡C—R. In some embodiments, A is phenyl substituted with —CH═CH—R. Insome embodiments, A is phenyl substituted with —C═C—R. In still furtherembodiments, —R is a cyclic ring selected from the group consisting ofbenzene, pyridine, pyridin-2-one, pyrazole, benzodioxole, and3,4-dihydroquinolin-2-one. In still further embodiments, —R is a cyclicring selected from the group consisting of benzene, pyridine,pyridin-2-one, pyrazole, benzodioxole, and 3,4-dihydroquinolin-2-one,wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ais pyridine, optionally substituted with one or two substituentsselected from the group consisting of C₁₋₃ alkyl, halogen, benzyloxy,—R, —CH═CH—R, and —C≡C—R. In further embodiments, A is pyridinesubstituted with —R. In some embodiments, A is pyridine substituted with—CH═CH—R or —C≡C—R. In some embodiments, A is pyridine substituted with—CH═CH—R. In some embodiments, A is pyridine substituted with —C≡C—R. Instill further embodiments, —R is a cyclic ring selected from the groupconsisting of benzene, pyridine, pyridin-2-one, pyrimidine, pyrazole,benzodioxole, benzoxadiazole, benzothiazole, indazole,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene. In still furtherembodiments, —R is a cyclic ring selected from the group consisting ofbenzene, pyridine, pyridin-2-one, pyrimidine, pyrazole, benzodioxole,benzoxadiazole, benzothiazole, indazole, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,1,4-dihydroquinazolin-2-one, 1H-pyrrolo[2,3-b]pyridine, benzoxazole, andthiophene, wherein said cyclic ring is optionally substituted with oneto three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ais thiophene, optionally substituted with one or two substituentsselected from the group consisting of C₁₋₃ alkyl, halogen, benzyloxy,—R, —CH═CH—R, and —C≡C—R. In further embodiments, A is thiophenesubstituted with —R. In some embodiments, A is thiophene substitutedwith —CH═CH—R or —C≡C—R. In some embodiments, A is thiophene substitutedwith —CH═CH—R. In some embodiments, A is thiophene substituted with—C≡C—R. In still further embodiments, —R is a cyclic ring selected fromthe group consisting of benzene, pyridine, tetrahydropyridine,pyridin-2-one, pyrimidine, imidazole, pyrazole, benzodioxole,benzoxadiazole, benzothiazole, indazole, 1,3-dihydroindol-2-one,quinolin-2-one, 3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,2,3-dihydro-1,4-benzoxazine, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,pyrido[2,3-b][1,4]oxazin-2-one, and 1,4-dihydroquinazolin-2-one. Instill further embodiments, —R is a cyclic ring selected from the groupconsisting of benzene, pyridine, tetrahydropyridine, pyridin-2-one,pyrimidine, imidazole, pyrazole, benzodioxole, benzoxadiazole,benzothiazole, indazole, 1,3-dihydroindol-2-one, quinolin-2-one,3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,2,3-dihydro-1,4-benzoxazine, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,pyrido[2,3-b][1,4]oxazin-2-one, and 1,4-dihydroquinazolin-2-one; whereinsaid cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl,acetylpiperazinyl, morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ais benzothiophene, optionally substituted with one or two substituentsselected from the group consisting of C₁₋₃ alkyl, halogen, benzyloxy,—R, —CH═CH—R, and —C≡C—R. In further embodiments, A is benzothiophenesubstituted with —R. In some embodiments, A is benzothiophenesubstituted with —CH═CH—R or —C≡C—R. In some embodiments, A isbenzothiophene substituted with —CH═CH—R. In some embodiments, A isbenzothiophene substituted with —C≡C—R. In still further embodiments, —Ris a cyclic ring selected from the group consisting of benzene,pyridine, pyridin-2-one, pyrazole, benzodioxole, and3,4-dihydroquinolin-2-one. In still further embodiments, —R is a cyclicring selected from the group consisting of benzene, pyridine,pyridin-2-one, pyrazole, benzodioxole, and 3,4-dihydroquinolin-2-one;wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl,acetylpiperazinyl, morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

Further, in the compound of Formulas X, Y, or 1, or the stereoisomerthereof, or its pharmaceutically acceptable salt thereof according tothe present technology, said aryl or heteroaryl group may preferably besubstituted with one or two substituents selected from the groupconsisting of C₁₋₃ alkyl, halogen, and —R. Preferably, said R may be acyclic ring selected from the group consisting of benzene, pyridine,pyridin-2-one, pyrazole, and 3,4-dihydroquinolin-2-one. More preferably,said cyclic ring may be substituted with a substituent selected from thegroup consisting of C₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆ alkylamino,and piperazinyl.

In one embodiment of the present technology, a compound, wherein n is 0;A is phenyl; said phenyl is substituted with one or two substituentsselected from the group consisting of halogen and —R; said R is a cyclicring selected from the group consisting of benzene, pyridine,3,4-dihydroquinolin-2-one, and pyrazole; and said cyclic ring issubstituted with a substituent selected from the group consisting ofC₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆ alkylamino, and piperazinyl; ora pharmaceutically acceptable salt thereof is provided.

In another embodiment of the present technology, a compound wherein n is0; wherein A is pyridine; wherein said pyridine is substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, and —R; wherein said R is a cyclic ring selected from the groupconsisting of benzene, pyridine, 3,4-dihydroquinolin-2-one, andpyrazole;

wherein said cyclic ring is substituted with a substituent selected fromthe group consisting of C₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆alkylamino, and piperazinyl, or a pharmaceutically acceptable saltthereof is provided.

In another embodiment of the present technology, a compound wherein n is0; A is thiophene; wherein said thiophene is substituted with one or twocyclic rings selected from the group consisting of benzene, pyridine,pyridin-2-one, 3,4-dihydroquinolin-2-one, and pyrazole; and said cyclicring is substituted with a substituent selected from the groupconsisting of C₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆ alkylamino, andpiperazinyl; or a pharmaceutically acceptable salt thereof is provided.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted benzene. In some embodiments, R isbenzene substituted with one to three substituents selected from thegroup consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, pyrrolidinonyl,and pyrrolidinyl. In some embodiments, R is benzene substituted with oneto three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted pyridine. In some embodiments, R ispyridine substituted with one to three substituents selected from thegroup consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted tetrahydropyridine. In some embodiments,R is tetrahydropyridine, optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted pyridin-2-one. In some embodiments, R ispyridin-2-one, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted pyrimidine. In some embodiments, R ispyrimidine, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted imidazole. In some embodiments, R isimidazole, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted pyrazole. In some embodiments, R ispyrazole, optionally substituted with one to three substituents selectedfrom the group consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted benzodioxole. In some embodiments, R isbenzodioxole, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted benzoxadiazole. In some embodiments, Ris benzoxadiazole, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted benzothiazole. In some embodiments, R isbenzothiazole, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted indazole. In some embodiments, R isindazole, optionally substituted with one to three substituents selectedfrom the group consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 1,3-dihydroindol-2-one. In someembodiments, R is 1,3-dihydroindol-2-one, optionally substituted withone to three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted quinolin-2-one. In some embodiments, Ris quinolin-2-one, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 3,4-dihydroisoquinolin-1-one. In someembodiments, R is 3,4-dihydroisoquinolin-1-one, optionally substitutedwith one to three substituents selected from the group consisting ofhalogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl,benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 3,4-dihydroquinolin-2-one. In someembodiments, R is 3,4-dihydroquinolin-2-one, optionally substituted withone to three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 3,4-dihydro-1,4-benzoxazine. In someembodiments, R is 3,4-dihydro-1,4-benzoxazine, optionally substitutedwith one to three substituents selected from the group consisting ofhalogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl,benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 2,3-dihydro-1,4-benzoxazine. In someembodiments, R is 2,3-dihydro-1,4-benzoxazine, optionally substitutedwith one to three substituents selected from the group consisting ofhalogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl,benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 1,4-benzoxazin-3-one. In someembodiments, R is 1,4-benzoxazin-3-one, optionally substituted with oneto three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 1,4-dihydro-3,1-benzoxazin-2-one. Insome embodiments, R is 1,4-dihydro-3,1-benzoxazin-2-one, optionallysubstituted with one to three substituents selected from the groupconsisting of halogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl,(cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 5,6,7,8-tetrahydronaphthyridine. In someembodiments, R is 5,6,7,8-tetrahydronaphthyridine, optionallysubstituted with one to three substituents selected from the groupconsisting of halogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl,(cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted triazolo[1,5-a]pyridine. In someembodiments, R is triazolo[1,5-a]pyridine, optionally substituted withone to three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 2,3-dihydro-pyrido[2,3-b][1,4]oxazine.In some embodiments, R is 2,3-dihydro-pyrido[2,3-b][1,4]oxazine,optionally substituted with one to three substituents selected from thegroup consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 3,4-dihydro-pyrido[3,2-b][1,4]oxazine.In some embodiments, R is 3,4-dihydro-pyrido[3,2-b][1,4]oxazine,optionally substituted with one to three substituents selected from thegroup consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted pyrido[2,3-b][1,4]oxazin-2-one. In someembodiments, R is pyrido[2,3-b][1,4]oxazin-2-one, optionally substitutedwith one to three substituents selected from the group consisting ofhalogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl,benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted pyrido[3,2-b][1,4]oxazin-3-one. In someembodiments, R is pyrido[3,2-b][1,4]oxazin-3-one, optionally substitutedwith one to three substituents selected from the group consisting ofhalogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl,benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 1,4-dihydroquinazolin-2-one. In someembodiments, R is 1,4-dihydroquinazolin-2-one, optionally substitutedwith one to three substituents selected from the group consisting ofhalogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl,benzyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted 1H-pyrrolo[2,3-b]pyridine. In someembodiments, R is 1H-pyrrolo[2,3-b]pyridine, optionally substituted withone to three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl,C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆alkylamino, C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted benzoxazole. In some embodiments, R isbenzoxazole, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In some embodiments of a compound of Formulas X, Y, or 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, Ris substituted or unsubstituted thiophene. In some embodiments, R isthiophene, optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

In another aspect, provided herein is a compound of Formula 12

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl group or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments of a compound of Formula 12, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² isphenyl substituted with triazolyl, C₁₋₆ alkylsulfonyl, or piperazinyl.In other embodiments, R² is benzodioxole or 3,4-dihydroquinolin-2-one,wherein said 3,4-dihydroquinolin-2-one is optionally substituted withC₁₋₆ alkyl.

In some embodiments of a compound of Formula 12, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted withtrifluoromethyl or mono- or di-C₁₋₆ alkylamino. In other embodiments, R²is substituted or unsubstituted pyrazole. In further embodiments, R² ispyrazole substituted with C₁₋₆ alkyl or difluoromethyl.

In another aspect, provided herein is a compound of Formula 13

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aralkoxy group, a substituted orunsubstituted aryl group, or a substituted or unsubstituted heterocyclicgroup, wherein said heterocyclic group has 1 to 5 heteroatom ringmembers chosen from O, N, or S, and said heterocyclic group is aromaticor non-aromatic.

In some embodiments of a compound of Formula 13, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aralkoxy group. In further embodiments, R²is substituted or unsubstituted benzyloxy.

In some embodiments of a compound of Formula 13, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² isphenyl substituted with C₁₋₆ alkylsulfonyl or piperazinyl. In otherembodiments, R² is benzodioxole or 3,4-dihydroquinolin-2-one, whereinsaid 3,4-dihydroquinolin-2-one is optionally substituted with C₁₋₆alkyl.

In some embodiments of a compound of Formula 13, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted with mono- ordi-C₁₋₆ alkylamino. In other embodiments, R² is substituted orunsubstituted pyrazole. In further embodiments, R² is pyrazolesubstituted with C₁₋₆ alkyl.

In some embodiments of a compound of Formula 13, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is substitutedor unsubstituted pyridin-2-one. In further embodiments, R² ispyridin-2-one substituted with C₁₋₆ alkyl.

In another aspect, provided herein is a compound of Formula 14

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

In some embodiments of a compound of Formula 14, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, the compound isof Formula 14a

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

In some embodiments of a compound of Formula 14, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, the compound isof Formula 14b

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

In some embodiments of a compound of Formula 14, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, the compound isof Formula 14c

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

In some embodiments of a compound of Formula 14, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² isphenyl substituted with one to three substituents selected from thegroup consisting of with halogen, C₁₋₆ alkoxy, mono- or di-C₁₋₆alkylamino, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl,morpholinylcarbonyl, piperazinyl, morpholinyl, pyrazolyl, C₁₋₆alkylpyrazolyl, triazolyl, and pyrrolidinonyl. In other embodiments, R²is benzodioxole, benzoxadiazole, benzothiazole, indazole,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 1,4-dihydroquinazolin-2-one,3,4-dihydroquinolin-2-one, or benzoxazole, wherein R² is optionallysubstituted with C₁₋₆ alkyl or amino.

In some embodiments of a compound of Formula 14, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted with C₁₋₆ alkoxy,trifluoromethyl, piperazinyl, morpholinyl, or mono- or di-C₁₋₆alkylamino. In other embodiments, R² is pyrimidine,1H-pyrrolo[2,3-b]pyridine, pyrazole, or thiophene, wherein R² isoptionally substituted with C₁₋₆ alkyl, difluoromethyl, C₁₋₆ alkoxy-C₁₋₆alkylamino, or C₁₋₆ alkylcarbonyl.

In some embodiments of a compound of Formula 14, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is substitutedor unsubstituted pyridin-2-one. In further embodiments, R² ispyridin-2-one substituted with C₁₋₆ alkyl.

In another aspect, provided herein is a compound of Formula 15

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S group.

In some embodiments of a compound of Formula 15, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² is2,3-dihydro-1,4-benzoxazine or 3,4-dihydroquinolin-2-one, wherein said3,4-dihydroquinolin-2-one is optionally substituted with C₁₋₆ alkyl.

In some embodiments of a compound of Formula 15, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted with morpholinylor mono- or di-C₁₋₆ alkylamino. In other embodiments, R² is2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, or pyrazole, wherein said pyrazole isoptionally substituted with C₁₋₆ alkyl.

In another aspect, provided herein is a compound of Formula 16

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments of a compound of Formula 16, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² isphenyl substituted with C₁₋₆ alkylsulfonyl or piperazinyl. In otherembodiments, R² is benzodioxole or 3,4-dihydroquinolin-2-one, whereinsaid 3,4-dihydroquinolin-2-one is optionally substituted with C₁₋₆alkyl.

In some embodiments of a compound of Formula 16, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted withtrifluoromethyl or mono- or di-C₁₋₆ alkylamino. In other embodiments, R²is substituted or unsubstituted pyrazole. In further embodiments, R² ispyrazole substituted with C₁₋₆ alkyl.

In another aspect, provided herein is a compound of Formula 17

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

In some embodiments of a compound of Formula 17, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² isphenyl substituted with one to three substituents selected from thegroup consisting of C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkylsulfonyl,mono- or di-C₁₋₆ alkylaminosulfonyl, mono- or di-C₁₋₆alkylaminocarbonyl, morpholinylcarbonyl, pyrazolyl, triazolyl,piperazinyl, and acetylpiperazinyl. In some embodiments, R² is phenylsubstituted with one to three substituents selected from the groupconsisting of C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkylsulfonyl, mono-or di-C₁₋₆ alkylaminosulfonyl, mono- or di-C₁₋₆ alkylaminocarbonyl,morpholinylcarbonyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl,piperazinyl, and acetylpiperazinyl. In other embodiments, R² is3,4-dihydroisoquinolin-1-one, quinolin-2-one,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 1,4-dihydroquinazolin-2-one,benzothiazole, benzoxadiazole, indazole, benzodioxole,1,3-dihydroindol-2-one, or 3,4-dihydroquinolin-2-one; wherein R² isoptionally substituted with C₁₋₆ alkyl, C₁₋₆ alkylcarbonylamino, orhalogen.

In some embodiments of a compound of Formula 17, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted with one to threesubstituents selected from the group consisting of halogen,trifluoromethyl, C₁₋₆ alkoxy, piperazinyl and mono- or di-C₁₋₆alkylamino. In other embodiments, R² is substituted or unsubstitutedpyrazole. In further embodiments, R² is pyrazole substituted with C₁₋₆alkyl, difluoromethyl, benzyl, (cycloalkyl)alkyl, alkylsulfonyl, orcycloalkylsulfonyl. In other embodiments, R² is5,6,7,8-tetrahydronaphthyridine, pyrimidine, imidazole, ortriazolo[1,5-a]pyridine; wherein R² is optionally substituted with oneto three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, C₁₋₆ alkoxy, amino, and C₁₋₆ alkoxy-C₁₋₆ alkylamino.

In some embodiments of a compound of Formula 17, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² istetrahydropyridine or pyridin-2-one, wherein said tetrahydropyridine andsaid pyridin-2-one are optionally substituted with C₁₋₆ alkyl or C₁₋₆alkylcarbonyl.

In another aspect, provided herein is a compound of Formula 18

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments of a compound of Formula 18, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In other embodiments, R² is2,3-dihydro-1,4-benzoxazine or 3,4-dihydroquinolin-2-one.

In some embodiments of a compound of Formula 18, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted with morpholinylor mono- or di-C₁₋₆ alkylamino. In other embodiments, R² is substitutedor unsubstituted pyrazole. In further embodiments, R² is pyrazolesubstituted with C₁₋₆ alkyl. In other embodiments, R² is2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,or pyrido[3,2-b][1,4]oxazin-3-one.

In another aspect, provided herein is a compound of Formula 19

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

In some embodiments of a compound of Formula 19, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² isphenyl substituted with C₁₋₆ alkylsulfonyl or piperazinyl. In otherembodiments, R² is benzodioxole or 3,4-dihydroquinolin-2-one; wherein R²is optionally substituted with C₁₋₆ alkyl.

In some embodiments of a compound of Formula 19, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted withtrifluoromethyl or mono- or di-C₁₋₆ alkylamino. In other embodiments, R²is substituted or unsubstituted pyrazole. In further embodiments, R² ispyrazole substituted with C₁₋₆ alkyl.

In another aspect, provided herein is a compound of Formula 20

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

In some embodiments of a compound of Formula 20, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted aryl group. In further embodiments, R² issubstituted or unsubstituted phenyl. In still further embodiments, R² isphenyl substituted with C₁₋₆ alkylsulfonyl or piperazinyl. In otherembodiments, R² is benzodioxole or 3,4-dihydroquinolin-2-one; wherein R²is optionally substituted with C₁₋₆ alkyl.

In some embodiments of a compound of Formula 20, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S. Infurther embodiments, R² is substituted or unsubstituted pyridine. Instill further embodiments, R² is pyridine substituted withtrifluoromethyl or mono- or di-C₁₋₆ alkylamino. In other embodiments, R²is substituted or unsubstituted pyrazole. In further embodiments, R² ispyrazole substituted with C₁₋₆ alkyl.

In some embodiments of a compound of Formula 20, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, R² is asubstituted or unsubstituted pyridine-2-one. In further embodiments, R²is pyridine-2-one substituted with C₁₋₆ alkyl.

In some embodiments of a compound of Formulas 12, 13, 14, 15, 16, 17,18, 19, or 20, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, R¹ is hydrogen.

In some embodiments of a compound of Formulas 12, 13, 14, 15, 16, 17,18, 19, or 20, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, R¹ is halogen.

In some embodiments of a compound of Formulas 12, 13, 14, 15, 16, 17,18, 19, or 20, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, R¹ is C₁₋₆ alkyl.

The compounds provided in the description are inhibitors of VAP-1. VAP-1inhibition may be measured, for example, by determining the half maximalinhibitory concentration (IC₅₀). One method for determining an IC₅₀ forVAP-1 is provided herein.

In one embodiment, the compounds are inhibitors of VAP-1. Selectivitymay be determined, for example, by comparing inhibition of VAP-1 toinhibition of other aminooxidaxes such as MAO-A (monoamine oxidase-A),MAO-B (monoamine oxidase-B), and DAO (diamine oxidase). In oneembodiment, said “significantly high inhibitory activity” means thatIC₅₀ for VAP-1 obtained from the in vitro enzyme assay test is at least3000 times lower than IC₅₀ of MAO-A, at least 100 times lower than IC₅₀of MAO-B, and at least 100 times lower than IC₅₀ of DAO. In analternative embodiment, “significantly high inhibitory activity” meansthe IC₅₀ for VAP-1 obtained from the in vitro enzyme analysis (in vitroenzyme assay) test is at least 3000 times lower than IC₅₀ of MAO-A, atleast 100 times lower than IC₅₀ of MAO-B, or at least 100 times lowerthan IC₅₀ of DAO.

In another aspect, a compound of Formulas X, Y, or 1, or a stereoisomerthereof, or a pharmaceutically acceptable salt thereof is selected fromthe following compounds or a pharmaceutically acceptable salt thereof:

-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3-bromophenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3,4-difluorophenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-3-fluoro-phenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-methyl-phenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(2-bromo-4-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-methyl-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-4-methyl-3-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-5-methyl-3-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-fluoro-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-methyl-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromopyrazin-2-yl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1,2,4-triazol-3-one;-   6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-3-fluoro-phenyl]-1,2,4-triazol-3-one;    2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-3-fluoro-phenyl]-1,2,4-triazol-3-one;    6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-fluoro-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;    2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-3-fluoro-phenyl]-1,2,4-triazol-3-one;    2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-fluoro-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-fluoro-phenyl]-1,2,4-triazol-3-one;-   6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-fluoro-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-fluoro-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-3-pyridyl]-1,2,4-triazol-3-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   6-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-4-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-methylsulfonylphenyl)-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-piperazin-1-ylphenyl)-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[6-(dimethylamino)-3-pyridyl]-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1,3-benzodioxol-5-yl)-4-pyridyl]-1,2,4-triazol-3-one;-   6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1-ethylpyrazol-4-yl)-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-5-methyl-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-5-methyl-3-pyridyl]-1,2,4-triazol-3-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-methylsulfonylphenyl)-pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-piperazin-1-ylphenyl)pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(trifluoromethyl)-3-pyridyl]pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)pyrazin-2-yl]-1,2,4-triazol-3-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]pyrazin-2-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-benzyloxyphenyl)methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-2-thienyl)methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-bromo-2-thienyl)methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-3-methyl-2-thienyl)methyl]-1,2,4-triazol-3-one;-   4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-methyl    sulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N,N-dimethyl-benzenesulfonamide;-   4-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N-methyl-benzamide;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3,4,5-trimethoxyphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   4-[[5-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-morpholine-4-carbonyl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-pyrazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-methoxy-3-pyridyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-piperazin-1-yl-3-pyridyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-5-fluoro-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-aminopyrimidin-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-ethoxypyrimidin-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-chloro-3-methyl-imidazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-pyridin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-ethyl-pyridin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-isopropyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-indazol-6-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-([1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2,1,3-benzoxadiazol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-7-fluoro-indolin-2-one;-   N-[6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,3-benzothiazol-2-yl]acetamide;-   7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-2H-isoquinolin-1-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4H-1,4-benzoxazin-3-one;-   7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4-methyl-1,4-benzoxazin-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methyl    sulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one;-   7-[(E)-2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]vinyl]-1H-pyrido[2,3-b][1,4]oxazin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-1H-pyrido[2,3-b][1,4]oxazin-2-one;-   7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-4H-pyrido[3,2-b][1,4]oxazin-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(2-thienyl)ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methyl    sulfonylphenyl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-piperazin-1-ylphenyl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1,3-benzodioxol-5-yl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1-ethylpyrazol-4-yl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N,N-dimethyl-benzamide;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3-methyl-1,4-dihydroquinazolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-isopropylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3-methyl-1,4-dihydroquinazolin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-isopropyl-pyridin-2-one;-   4-[[4-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-fluoro-1H-quinolin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-pyridin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3,4-dihydro-1H-quinolin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-isopropylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-[6-(trifluoromethyl)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1-ethylpyrazol-4-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   5-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-piperazin-1-yl-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[4-(morpholine-4-carbonyl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-morpholino-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(3-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[3-(dimethylamino)-4-fluoro-phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   5-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-ethyl-pyridin-2-one;-   7-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(6-piperazin-1-yl-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-4H-1,4-benzoxazin-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3,4,5-trimethoxyphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(6-methoxy-3-pyridyl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   4-[5-(2-amino-1,3-benzothiazol-5-yl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(2,1,3-benzoxadiazol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzoxazol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   4-[5-(5-acetyl-2-thienyl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-pyrazol-3-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1H-indazol-6-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[4-(morpholine-4-carbonyl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-morpholinophenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   4-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-N,N-dimethyl-benzenesulfonamide;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-1H-pyrido[2,3-b][1,4]oxazin-2-one;-   7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-4H-pyrido[3,2-b][1,4]oxazin-3-one;-   6-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-3-methyl-1,4-dihydroquinazolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[1-(difluoromethyl)pyrazol-4-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-isopropylpyrazol-4-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)-2-methyl-phenyl]-1,2,4-triazol-3-one;-   6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[1-(difluoromethyl)pyrazol-4-yl]-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-isopropylpyrazol-4-yl)-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[3-(1H-1,2,4-triazol-3-yl)phenyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   6-[4-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   5-[4-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   6-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4-dihydroquinolin-2-one;-   5-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4-dihydroquinolin-2-one;-   5-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[4-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[3-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-pyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-cyclopropylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(cyclopropylmethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-benzylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-(2-(aminomethyl)-3,3-difluoroallyl)-4-((5-(6-(dimethylamino)pyridin-3-yl)-3-fluorothiophen-2-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one;    and-   6-(5-((1-(2-(aminomethyl)-3,3-difluoroallyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)methyl)-4-fluorothiophen-2-yl)-8-methyl-3,4-dihydroquinolin-2(1H)-one.

As for the compound of Formula 1, or its stereoisomer, or itspharmaceutically acceptable salt, the more preferred compound may be acompound selected from the group consisting of the following compoundsor a pharmaceutically acceptable salt thereof:

-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazol-3-one;    and-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazol-3-one.

The compound of Formula 1 of the present technology can be in the formof a pharmaceutically acceptable salt. The term “pharmaceuticallyacceptable salt,” as used herein, represents salts or zwitterionic formsof the compounds of the present technology which are water oroil-soluble or dispersible; which are suitable for treatment of diseaseswithout undue toxicity, irritation, and allergic-response; which arecommensurate with a reasonable benefit/risk ratio; and which areeffective for their intended use. The salts can be prepared during thefinal isolation and purification of the compounds or separately by, forexample, reacting the appropriate compound in the form of the free basewith a suitable acid. Such salts include conventional acid additionsalts, e.g., a salt derived from inorganic acid such as hydrochloricacid, bromic acid, sulfuric acid, sulfamic acid, phosphoric acid, ornitric acid and a salt derived from organic acid such as acetic acid,propionic acid, succinic acid, glycolic acid, stearic acid, citric acid,maleic acid, malonic acid, methanesulfonic acid, tartaric acid, malicacid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid,2-acetoxybenzoic acid, fumaric acid, p-toluenesulfonic acid, oxalic acidor trifluoroacetic acid. Further, said salts include conventional metalsalt types, e.g., a salt derived from a metal such as lithium, sodium,potassium, magnesium, or calcium. Said acid addition salt or metal saltcan be prepared according to conventional methods.

The compound of Formulas X, Y, or 1, or the stereoisomer thereof, or asalt thereof according to the present technology may be prepared byvarious methods. For example, the compound of Formula 1, or astereoisomer thereof, or a salt thereof according to the presenttechnology can be prepared by a preparation process comprising the stepof reacting a compound of Formula 2 with a compound of Formula 3a or acompound of Formula 3b to obtain a compound of Formula 1a; and the stepof deprotecting said compound of Formula 1a.

In said Formulae 1, 1a, 2,3a and 3b, Boc is an amine protecting group(e.g., tert-butoxycarbonyl, 9-fluorenylmethyloxycarbonyl (FMOC),benzyloxycarbonyl (CBZ), triphenylmethyl (trityl), etc.), A′ is an arylor heteroaryl group selected from the group consisting of phenyl,pyridine, pyrazine, and thiophene; Z is a boronic acid (B(OH)₂) orboronic acid pinacol ester, R′ is one or two groups chosen from C₁₋₃alkyl, halogen, benzyloxy, —R, —CH═CH—R, or —C≡C—R, and A and R are thesame as defined above.

The reaction of the compound of Formula 2 above with a commerciallyavailable compound of Formula 3a may be carried out via Suzuki reaction.Said reaction can be carried out by using a palladium catalyst. Thepalladium catalyst includes palladium diacetate (Pd(OAc)₂),tris(dibenzylideneacetone)dipalladium (Pd₂(dba)₃),tetrakis(triphenylphosphine)palladium (Pd(PPh₃)₄) orpalladiumdi[1,1′-bis(diphenylphosphino)ferrocene]dichloride(PdCl₂(dppf)₂), etc. In the reaction carried out under a palladiumcatalyst, a ligand and a base can be added in addition to the palladiumcatalyst. Said ligand includes(S)-2,2-bis(diphenylphospino)-1,1-binaphthyl(BINAP),1,1′-bis(diphenylphospino)ferrocene (dppf), (tri-O-tolyl)phosphine(P(O-Tol)₃), or the like and said base includes an inorganic base suchas cesium carbonate (Cs₂CO₃), sodium carbonate (Na₂CO₃), potassiumcarbonate (K₂CO₃), potassium fluoride (KF), cesium fluoride (CsF),sodium hydroxide (NaOH), potassium phosphonate (K₃PO₄), sodiumtert-butoxide (tert-BuONa), potassium tert-butoxide (tert-BuOK), or thelike. The reaction may be carried out in a non-polar organic solventsuch as benzene or toluene, or a polar solvent such as dioxane,tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane,N,N-dimethylformamide, or the like, at a temperature ranging from 50° C.to 150° C., preferably from 80° C. to 110° C. Other reaction conditions,including e.g., reaction time, may be determined from the reactionconditions for conventional Suzuki reaction (Barbara Czako and LaszloKurti, STRATEGIC APPLICATIONS of NAMED REACTIONS in ORGANIC SYNTHESIS,2005). Further, the reaction of the compound of Formula 2 with acommercially available compound of Formula 3b (i.e., an ethynederivative) can be carried out via Sonogashira coupling reaction using apalladium reagent such as bis(triphenylphosphine)palladium(II)dichloride, tetrakis(triphenylphosphine)palladium(0), etc., and a copperiodide. The coupling reaction may be carried out at room temperature ora heated temperature, e.g., a temperature ranging from 20° C. to 60° C.In addition, in order to improve reaction rate and reaction yield, saidcoupling reaction can be carried out in the presence of a base such as adiisopropylamine, a triethylamine, etc., and a ligand such astriphenylphosphine or the like.

Deprotection of the compound of Formula 1a can be carried out accordingto conventional methods (e.g., Theodora W. Greene and Peter G. M. Wuts,Protective groups in organic synthesis, 3rd Ed., 1999). For example,said amine protecting group in an organic solvent such asdichloromethane, dioxane, ethyl acetate, etc., can be removed by usingan acid such as trifluoroacetate or hydrochloric acid gas at roomtemperature.

The compound of Formula 2 can be prepared according to the followingReaction Scheme 1.

In Reaction Scheme 1, A′, n, and Boc are the same as defined in theabove.

A compound of Formula 4 is commercially available. The compound ofFormula 4 can be converted to a compound of Formula 5 via nucleophilicacylsubstitution reaction. Said nucleophilic acylsubstitution reactioncan be carried out at 0° C. to room temperature by using pyridine,triethylamine, or the like in a solvent such as ethyl acetate,tetrahydrofuran, etc. (Chunquan Sheng; Xiaoying Che; Wenya Wang;Shengzheng Wang; Yongbing Cao; Zhenyuan Miao; Jianzhong Yao; WannianZhang, European Journal of Medicinal Chemistry, 46, 5276-5282, 2011).

The compound of Formula 5 can be converted to a compound of Formula 6via hydrazinolysis reaction. The hydrazinolysis reaction can be carriedout according to known methods (e.g., WO 2005/014583, etc.).

The compound of Formula 6 can be converted to a compound of Formula 10via cyclization reaction. The cyclization reaction can be carried out atroom temperature to 80° C. by using a formamidineacetate and an aceticacid in N,N-dimethylformamide or 1-propanol (Chunquan Sheng; XiaoyingChe; Wenya Wang; Shengzheng Wang; Yongbing Cao; Zhenyuan Miao; JianzhongYao; Wannian Zhang, European Journal of Medicinal Chemistry, 46,5276-5282, 2011).

In another method, the compound of Formula 4 can be converted to acompound of Formula 10 via cyclization reaction with a compound ofFormula 7. Said cyclization reaction can be performed in a solvent suchas methanol, N,N-dimethylformamide, or the like, by using sodiummethoxide or potassium hydroxide at a temperature between 50° C. to 150°C. The compound of Formula 7 above can be prepared by formylationreaction of a commercially available ethyl carbazate. Said formylationreaction may preferably be orthoester reaction, which can be carriedout, for example, by using triethyl orthoformate or trimethylorthoformate. Said formylation reaction can be performed in a solventsuch as methanol, N,N-dimethylformamide, or the like at a temperaturebetween 80° C.−150° C.

In another method, the compound of Formula 8 also can be converted to acompound of Formula 10 via C—N alkylation reaction with a compound ofFormula 9. The compound of Formula 8 and Formula 9 are both commerciallyavailable. Said alkylation reaction can be performed in organic solventsuch as N,N-dimethylformamide or the like, by using sodium hydride orpotassium carbonate at a temperature between 20° C. to 60° C.

The reaction of the compound of Formula 10 above with a compound ofFormula 11 can be carried out via Mitsunobu reaction. For example, saidreaction can be carried out in the presence of triphenylphosphine ortrin-butylphosphine using diethyl azodicarboxylate (DEAD) or diisopropylazodicarboxylate (DIAD). The reaction solvent may be a polar organicsolvent such as dichloromethane, dioxane, tetrahydrofuran,dimethylformamide, etc. The reaction may be carried out at 0° C. to roomtemperature, and can be carried out at a higher temperature on occasion.Other reaction conditions including reaction time may be determined fromthe reaction conditions for conventional Mitsunobu reaction (BarbaraCzako and Laszlo Kurti, STRATEGIC APPLICATIONS of NAMED REACTIONS inORGANIC SYNTHESIS, 2005).

The compound of Formula 11 can be prepared according to the followingReaction Scheme 2.

In Reaction Scheme 2, TBDMS is tert-butyldimethylsilyl, which is ahydroxyl protecting group and Boc is the same as defined in the above.

A compound of Formula 11a is commercially available and can be preparedaccording to known methods (e.g., WO 2013/163675, etc.). The compound ofFormula 11a can be converted to a compound of Formula 11b viagem-difluoroolefination reaction. The gem-difluoroolefination reactioncan be carried out in the presence of a base such as potassiumtert-butoxide (tert-BuOK), lithium bis(trimethylsilyl)amide (LiHMDS), orthe like using a fluorinated sulfone such as difluoromethyl 2-pyridylsulfone. The reaction solvent may be an organic solvent such asdimethylformamide, tetrahydrofuran, or the like and the reaction can becarried out at a temperature between −40° C.-0° C. (Yanchuan Zhao;Weizhou Huang; Lingui Zhu; Jinbo Hu, Organic Letters, 12, 1444-1447,2010), etc.

The compound of Formula 1b can be converted to a compound of Formula 11via deprotection reaction of a hydroxyl protecting group (TBDMS). Thedeprotection reaction of a hydroxyl protecting group can be carried outaccording to known methods (Theodora W. Greene and Peter G. M. Wuts,Protective groups in organic synthesis, 3rd Ed., 1999). For example, thedeprotection group of a hydroxyl protecting group (TBDMS) can be carriedout in a solvent such as dichloromethane, tetrahydrofuran, or the like,using an organic salt such as tetrabutylamoniumfluoride (TBAF), etc., atroom temperature.

The 3,3-difluoroallylamines according to the present technology, i.e., acompound of Formulas X, Y, 1, 12, 13, 14, 15, 16, 17, 18, 19, or 20, ora stereoisomer thereof, or a pharmaceutically acceptable salt thereof,have an inhibitory activity on VAP-1, and thus can be usefully appliedin the prevention or treatment of a disease mediated by VAP-1.Preferably, the compound of Formulas X, Y, 1, 12, 13, 14, 15, 16, 17,18, 19, or 20, according to the present technology, or a stereoisomerthereof, or a pharmaceutically acceptable salt thereof can be usefullyapplied for the prevention of treatment of nonalcoholic steatohepatitis(NASH).

In some embodiments, provided herein is the use of the3,3-difluoroallylamines according to the present technology, i.e., thecompound of Formulas X, Y, 1, 12, 13, 14, 15, 16, 17, 18, 19, or 20, ora stereoisomer thereof, or a pharmaceutically acceptable salt thereof,in the preparation of a medicament for the prophylaxis and/or treatmentof lipid and lipoprotein disorders (such as, but not limited to,hypercholesterolemia, hypertriglyceridemia, and atherosclerosis), ofconditions and diseases which result from chronic fatty and fibroticdegeneration of organs due to accumulated lipid and specificallytriglyceride accumulation and subsequent activation of profibroticpathways (such as, but not limited to, NASH and chronic cholestaticconditions in the liver, Glomerulosclerosis and Diabetic Nephropathy inthe kidney, Macular Degeneration and Diabetic Retinopathy in the eye andneurodegenerative diseases, such as Alzheimer's Disease in the brain, orDiabetic Neuropathies in the peripheral nervous system), of Type I orType II Diabetes and clinical complications of Type I and Type IIDiabetes (such as, but not limited to, Diabetic Nephropathy, DiabeticRetinopathy, Diabetic Neuropathies, or Peripheral Arterial OcclusiveDisease (PAOD)), of chronic intrahepatic or some forms of extrahepaticcholestatic conditions, of liver fibrosis, of acute intrahepticcholestatic conditions, of obstructive or chronic inflammatory disordersthat arise out of improper bile composition (such as, but not limitedto, cholelithiasis also known as cholesterol gallstones), ofgastrointestinal conditions with a reduced uptake of dietary fat andfat-soluble dietary vitamins, of inflammatory bowel diseases, of obesityand metabolic syndrome (combined conditions of dyslipidemia, diabetesand abnormally high body-mass index), of persistent infections byintracellular bacteria or parasitic protozoae, of non-malignanthyperproliferative disorders, of malignant hyperproliferative disorders(such as, but not limited to, different forms of cancer, specificallycertain forms of breast, liver or colon cancer, or a disorder selectedfrom the group consisting of hepatocellular carcinoma, colon adenoma,and polyposis), of colon adenocarcinoma and hepatocellular carcinoma inparticular, of liver steatosis and associated syndromes, of Hepatitis Binfection, of Hepatitis C infection and/or of cholestatic and fibroticeffects that are associated with alcohol-induced cirrhosis or withviral-borne forms of hepatitis, of liver failure or liver malfunction asan outcome of chronic liver diseases or of surgical liver resection, ofacute myocardial infarction, of acute stroke, of thrombosis which occursas an endpoint of chronic obstructive atherosclerosis, ofosteoarthritis, of rheumatoid arthritis, of psoriasis, or of cerebralinfarction, individually or of any combination thereof.

In some embodiments, the compounds and/or pharmaceutical compositionsdisclosed herein are used for prophylaxis and/or treatment of chronicintrahepatic conditions, such as Primary Biliary Cirrhosis (PBC),Primary Sclerosing Cholangitis (PSC), progressive familiar cholestasis(PFIC), alcohol-induced cirrhosis and associated cholestasis, and someforms of extrahepatic cholestatic conditions, or liver fibrosis.

In some embodiments, provided herein is a method to treat chronicintrahepatic conditions and/or some forms of extrahepatic cholestaticconditions in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein. In some embodiments, the chronic intrahepaticconditions are selected from PBC, PSC, PFIC, and alcohol-inducedcirrhosis and associated cholestasis.

In some embodiments, provided herein is a method to treat liver fibrosisin a patient in need thereof, the method comprising, consistingessentially of, or consisting of administering to the patient atherapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat a lipid andlipoprotein disorder in a patient in need thereof, the methodcomprising, consisting essentially of, or consisting of administering tothe patient a therapeutically effective amount of a compound or acomposition disclosed herein. In some embodiments, the lipid andlipoprotein disorder is selected from hypercholesterolemia,hypertriglyceridemia, and atherosclerosis.

In some embodiments, provided herein is a method to treat a condition ordisease which results from chronic fatty and fibrotic degeneration oforgans due to accumulated lipid and specifically triglycerideaccumulation and subsequent activation of profibrotic pathways in apatient in need thereof, the method comprising, consisting essentiallyof, or consisting of administering to the patient a therapeuticallyeffective amount of a compound or a composition disclosed herein. Insome embodiments, the condition or disease which results from chronicfatty and fibrotic degeneration of organs due to accumulated lipid andspecifically triglyceride accumulation and subsequent activation ofprofibrotic pathways is selected from NASH and chronic cholestaticconditions in the liver, Glomerulosclerosis and Diabetic Nephropathy inthe kidney, Macular Degeneration and Diabetic Retinopathy in the eye,and neurodegenerative diseases. In some further embodiments,neurodegenerative diseases are selected from Alzheimer's Disease in thebrain, and Diabetic Neuropathies in the peripheral nervous system.

In some embodiments, provided herein is a method to treat Type I or TypeII Diabetes and clinical complications of Type I and Type II Diabetes ina patient in need thereof, the method comprising, consisting essentiallyof, or consisting of administering to the patient a therapeuticallyeffective amount of a compound or a composition disclosed herein. Insome embodiments, provided herein is a method to treat Type I Diabetesin a patient in need thereof, the method comprising, consistingessentially of, or consisting of administering to the patient atherapeutically effective amount of a compound or a compositiondisclosed herein. In some embodiments, provided herein is a method totreat Type II Diabetes in a patient in need thereof, the methodcomprising, consisting essentially of, or consisting of administering tothe patient a therapeutically effective amount of a compound or acomposition disclosed herein. In some embodiments, provided herein is amethod to treat one or more clinical complications of Type I and Type IIDiabetes in a patient in need thereof, the method comprising, consistingessentially of, or consisting of administering to the patient atherapeutically effective amount of a compound or a compositiondisclosed herein. In some embodiments, the clinical complications ofType I and Type II Diabetes are selected from Diabetic Nephropathy,Diabetic Retinopathy, Diabetic Neuropathies, and Peripheral ArterialOcclusive Disease (PAOD), or any combination thereof.

In some embodiments, provided herein is a method to treat acuteintraheptic cholestatic conditions in a patient in need thereof, themethod comprising, consisting essentially of, or consisting ofadministering to the patient a therapeutically effective amount of acompound or a composition disclosed herein.

In some embodiments, provided herein is a method to treat obstructive orchronic inflammatory disorders that arise out of improper bilecomposition in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein. In some embodiments, the obstructive or chronicinflammatory disorders that arise out of improper bile composition ischolelithiasis also known as cholesterol gallstones.

In some embodiments, provided herein is a method to treatgastrointestinal conditions with a reduced uptake of dietary fat andfat-soluble dietary vitamins in a patient in need thereof, the methodcomprising, consisting essentially of, or consisting of administering tothe patient a therapeutically effective amount of a compound or acomposition disclosed herein.

In some embodiments, provided herein is a method to treat inflammatorybowel diseases in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat obesity andmetabolic syndrome in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat persistentinfections by intracellular bacteria or parasitic protozoae in a patientin need thereof, the method comprising, consisting essentially of, orconsisting of administering to the patient a therapeutically effectiveamount of a compound or a composition disclosed herein.

In some embodiments, provided herein is a method to treat non-malignanthyperproliferative disorders in a patient in need thereof, the methodcomprising, consisting essentially of, or consisting of administering tothe patient a therapeutically effective amount of a compound or acomposition disclosed herein.

In some embodiments, provided herein is a method to treat malignanthyperproliferative disorders in a patient in need thereof, the methodcomprising, consisting essentially of, or consisting of administering tothe patient a therapeutically effective amount of a compound or acomposition disclosed herein. In some embodiments, malignanthyperproliferative disorders are selected from different forms ofcancer, specifically certain forms of breast, liver or colon cancer, ora disorder selected from the group consisting of hepatocellularcarcinoma, colon adenoma, and polyposis.

In some embodiments, provided herein is a method to treat colonadenocarcinoma in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat hepatocellularcarcinoma in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat liversteatosis and associated syndromes in a patient in need thereof, themethod comprising, consisting essentially of, or consisting ofadministering to the patient a therapeutically effective amount of acompound or a composition disclosed herein.

In some embodiments, provided herein is a method to treat Hepatitis Binfection in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat Hepatitis Cinfection in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat cholestaticand fibrotic effects that are associated with alcohol-induced cirrhosisor with viral-borne forms of hepatitis in a patient in need thereof, themethod comprising, consisting essentially of, or consisting ofadministering to the patient a therapeutically effective amount of acompound or a composition disclosed herein.

In some embodiments, provided herein is a method to treat liver failureor liver malfunction as an outcome of chronic liver diseases or ofsurgical liver resection in a patient in need thereof, the methodcomprising, consisting essentially of, or consisting of administering tothe patient a therapeutically effective amount of a compound or acomposition disclosed herein.

In some embodiments, provided herein is a method to treat acutemyocardial infarction in a patient in need thereof, the methodcomprising, consisting essentially of, or consisting of administering tothe patient a therapeutically effective amount of a compound or acomposition disclosed herein.

In some embodiments, provided herein is a method to treat acute strokein a patient in need thereof, the method comprising, consistingessentially of, or consisting of administering to the patient atherapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat thrombosiswhich occurs as an endpoint of chronic obstructive atherosclerosis in apatient in need thereof, the method comprising, consisting essentiallyof, or consisting of administering to the patient a therapeuticallyeffective amount of a compound or a composition disclosed herein.

In some embodiments, provided herein is a method to treat osteoarthritisin a patient in need thereof, the method comprising, consistingessentially of, or consisting of administering to the patient atherapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat rheumatoidarthritis in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

In some embodiments, provided herein is a method to treat psoriasis in apatient in need thereof, the method comprising, consisting essentiallyof, or consisting of administering to the patient a therapeuticallyeffective amount of a compound or a composition disclosed herein.

In some embodiments, provided herein is a method to treat cerebralinfarction in a patient in need thereof, the method comprising,consisting essentially of, or consisting of administering to the patienta therapeutically effective amount of a compound or a compositiondisclosed herein.

Thus, the present technology includes a pharmaceutical composition forinhibiting vascular adhesion protein-1 (VAP-1), comprising atherapeutically effective amount of a compound of Formula 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof asan active ingredient. In one embodiment, the present technology providesa pharmaceutical composition for preventing or treating nonalcoholicsteatohepatitis (NASH), comprising a therapeutically effective amount ofa compound of Formula 1, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof as an active ingredient. Insome embodiments, provided herein is a pharmaceutical composition forpreventing or treating NASH comprising, consisting essentially of, orconsisting of a therapeutically effective amount of a compound ofFormula 1, or a stereoisomer thereof, or a pharmaceutically acceptablesalt thereof, and at least one pharmaceutically acceptable carrier orexcipient.

In another aspect, the present technology provides a pharmaceuticalcomposition for preventing or treating diabetic nephropathy comprising,consisting essentially of, or consisting of a therapeutically effectiveamount of a compound of Formula 1, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof, and at least onepharmaceutically acceptable carrier or excipient.

In another aspect, the present technology provides a pharmaceuticalcomposition for preventing or treating primary sclerosing cholangitiscomprising, consisting essentially of, or consisting of atherapeutically effective amount of a compound of Formula 1, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, andat least one pharmaceutically acceptable carrier or excipient.

In some embodiments, the compounds of the present disclosure may becombined with one or more additional therapies for the prevention ortreatment of a disease or condition amenable to treatment by inhibitionof VAP-1.

In some embodiments, the compositions disclosed herein contain at leastone additional active agent.

Exemplary additional active agents include, but are not limited, one ormore of a(n) ACE inhibitor, Acetyl CoA carboxylase inhibitor, AdenosineA3 receptor agonist, Adiponectin receptor agonist, AKT protein kinaseinhibitor, AMP-activated protein kinases (AMPK), Amylin receptoragonist, Angiotensin II AT-1 receptor antagonist, Apoptosis SignalingKinase 1 inhibitor, Autotaxin inhibitors, Bioactive lipid, Calcitoninagonist, Caspase inhibitor, Caspase-3 stimulator, Cathepsin inhibitor,Caveolin 1 inhibitor, CCR2 chemokine antagonist, CCR3 chemokineantagonist, CCR5 chemokine antagonist, Chloride channel stimulator, CNR1inhibitor, Cyclin D1 inhibitor, Cytochrome P450 7A1 inhibitor, DGAT1/2inhibitor, Dipeptidyl peptidase IV inhibitor, Endosialin modulator,Eotaxin ligand inhibitor, Extracellular matrix protein modulator,Farnesoid X receptor agonist, Fatty acid synthase inhibitors, FGF 1receptor agonist, Fibroblast growth factor (FGF-15, FGF-19, FGF-21)ligands, Galectin-3 inhibitor, Glucagon receptor agonist, Glucagon-likepeptide 1 agonist, G-protein coupled bile acid receptor 1 agonist,Hedgehog (Hh) modulator, Hepatitis C virus NS3 protease inhibitor,Hepatocyte nuclear factor 4 alpha modulator (HNF4A), Hepatocyte growthfactor modulator, HMG CoA reductase inhibitor, IL-10 agonist, IL-17antagonist, Ileal sodium bile acid cotransporter inhibitor, Insulinsensitizer, integrin modulator, intereukin-1 receptor-associated kinase4 (IRAK4) inhibitor, Jak2 tyrosine kinase inhibitor, ketohexokinaseinhibitors, Klotho beta stimulator, 5-Lipoxygenase inhibitor,Lipoprotein lipase inhibitor, Liver X receptor, LPL gene stimulator,Lysophosphatidate-1 receptor antagonist, Lysyl oxidase homolog 2inhibitor, Matrix metalloproteinases (MMPs) inhibitor, MEKK-5 proteinkinase inhibitor, Membrane copper amine oxidase (VAP-1) inhibitor,Methionine aminopeptidase-2 inhibitor, Methyl CpG binding protein 2modulator, MicroRNA-21(miR-21) inhibitor, Mitochondrial uncoupler,Myelin basic protein stimulator, NACHT LRR PYD domain protein 3 (NLRP3)inhibitor, NAD-dependent deacetylase sirtuin stimulator, NADPH oxidaseinhibitor (NOX), Nicotinic acid receptor 1 agonist, P2Y13 purinoceptorstimulator, PDE 3 inhibitor, PDE 4 inhibitor, PDE 5 inhibitor, PDGFreceptor beta modulator, Phospholipase C inhibitor, PPAR alpha agonist,PPAR delta agonist, PPAR gamma agonist, PPAR gamma modulator,Protease-activated receptor-2 antagonist, Protein kinase modulator, Rhoassociated protein kinase inhibitor, Sodium glucose transporter-2inhibitor, SREBP transcription factor inhibitor, STAT-1 inhibitor,Stearoyl CoA desaturase-1 inhibitor, Suppressor of cytokine signalling-1stimulator, Suppressor of cytokine signalling-3 stimulator, Transforminggrowth factor β (TGF-β), Transforming growth factor β activated Kinase 1(TAK1), Thyroid hormone receptor beta agonist, TLR-4 antagonist,Transglutaminase inhibitor, Tyrosine kinase receptor modulator, GPCRmodulator, nuclear hormone receptor modulator, WNT modulators, andYAP/TAZ modulator. Examples of JAK inhibitors include, but are notlimited to, filgotonib and tofacitinib. A non-limiting example of anapoptosis signal kinase inhibitor is selonsertib.

The compound of Formula 1, or the stereoisomer thereof, or thepharmaceutically acceptable salt thereof, and at least one additionalactive agent may be administered in any order or even simultaneously.The multiple active agents may be provided in a single, unified form, orin multiple forms (by way of example only, either as a single pill or astwo separate pills). One of the active agents may be given in multipledoses, or both may be given as multiple doses. If not simultaneous, thetiming between the multiple doses may vary from more than zero weeks toless than four weeks. In addition, the combination methods, compositionsand formulations are not to be limited to the use of only two agents.

The pharmaceutical composition of the present technology may comprise apharmaceutically acceptable carrier, such as diluents, disintegrants,sweetening agents, glidants, or flavoring agents and may be formulatedinto an oral dosage form such as tablets, capsules, powders, granules,suspensions, emulsions, or syrups; or a parenteral dosage form such asliquids for external use, suspensions for external use, emulsions forexternal use, gels (ointments or the like), inhaling agents, sprayingagents, injections, etc. Said dosage forms may be formulated in variousforms, e.g., a dosage form for single administration or for multipleadministrations.

The pharmaceutical composition of the present technology may includeexcipients such as lactose, corn starch, or the like, glidants such asmagnesium stearate, etc., emulsifying agents, suspending agents,stabilizers, and isotonic agents, etc. If desired, a sweetening agentand/or a flavoring agent may be added. Exemplary excipients include,without limitation, polyethylene glycol (PEG), hydrogenated castor oil(HCO), cremophors, carbohydrates, starches (e.g., corn starch),inorganic salts, antimicrobial agents, antioxidants, binders/fillers,surfactants, lubricants (e.g., calcium or magnesium stearate), glidantssuch as talc, disintegrants, diluents, buffers, acids, bases, filmcoats, combinations thereof, and the like.

Specific carbohydrate excipients include, for example: monosaccharides,such as fructose, maltose, galactose, glucose, D-mannose, sorbose, andthe like; disaccharides, such as lactose, sucrose, trehalose,cellobiose, and the like; polysaccharides, such as raffinose,melezitose, maltodextrins, dextrans, starches, and the like; andalditols, such as mannitol, xylitol, maltitol, lactitol, xylitol,sorbitol (glucitol), pyranosyl sorbitol, myoinositol, and the like.

Inorganic salt or buffers include, but are not limited to, citric acid,sodium chloride, potassium chloride, sodium sulfate, potassium nitrate,sodium phosphate monobasic, sodium phosphate dibasic, and combinationsthereof.

Suitable antioxidants for use in the present disclosure include, forexample, ascorbyl palmitate, butylated hydroxyanisole, butylatedhydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate,sodium bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite,and combinations thereof.

Additional exemplary excipients include surfactants such aspolysorbates, e.g., “Tween 20” and “Tween 80,” and pluronics such as F68and F88 (both of which are available from BASF, Mount Olive, N.J.),sorbitan esters, lipids (e.g., phospholipids such as lecithin and otherphosphatidylcholines, and phosphatidylethanolamines), fatty acids andfatty esters, steroids such as cholesterol, and chelating agents, suchas EDTA, zinc and other such suitable cations.

Further, a composition disclosed herein may optionally include one ormore acids or bases. Non-limiting examples of acids that can be usedinclude those acids selected from the group consisting of hydrochloricacid, acetic acid, phosphoric acid, citric acid, malic acid, lacticacid, formic acid, trichloroacetic acid, nitric acid, perchloric acid,phosphoric acid, sulfuric acid, fumaric acid, and combinations thereof.Non-limiting examples of suitable bases include bases selected from thegroup consisting of sodium hydroxide, sodium acetate, ammoniumhydroxide, potassium hydroxide, ammonium acetate, potassium acetate,sodium phosphate, potassium phosphate, sodium citrate, sodium formate,sodium sulfate, potassium sulfate, potassium fumerate, and combinationsthereof.

The amount of any individual excipient in the composition will varydepending on the role of the excipient, the dosage requirements of theactive agent components, and particular needs of the composition.

Generally, however, the excipient will be present in the composition inan amount of about 1% to about 99% by weight, preferably from about 5%to about 98% by weight, more preferably from about 15 to about 95% byweight of the excipient. In general, the amount of excipient present ina composition of the disclosure is selected from the following: at leastabout 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,65%, 70%, 75%, 80%, 85%, 90%, or even 95% by weight.

The composition of the present technology can be administered orally orparenterally, including inhalation, intravenous, intraperitoneal,subcutaneous, rectal and topical routes of administration. Therefore,the composition of the present technology can be formulated into variousforms such as tablets, capsules, aqueous solutions, suspensions, or thelike. In the case of tablets for oral administration, carriers such aslactose, corn starch, and lubricating agents, e.g., magnesium stearate,can be conventionally added thereto. In the case of capsules for oraladministration, lactose and/or dried corn starch can be used as adiluent. When an aqueous suspension is required for oral administration,the active ingredient can be combined with emulsifying and/or suspendingagents. If desired, certain sweetening agents and/or flavoring agentscan be added thereto. For intramuscular, intraperitoneal, subcutaneousand intravenous administration, sterile solutions of the activeingredient are usually prepared, and the pH of the solutions should besuitably adjusted and buffered. For intravenous administration, thetotal concentration of solutes should be controlled in order to renderthe preparation isotonic. The composition of the present technology maybe in the form of an aqueous solution containing pharmaceuticallyacceptable carriers, e.g., saline having a pH level of 7.4. Thesolutions may be introduced into a patient's intramuscular blood-streamby local bolus injection.

Said 3,3-difluoroallylamines, i.e., a compound of Formula 1, or astereoisomer thereof, or its pharmaceutically acceptable salt can beadministered to a patient in an effective amount ranging from about0.001 mg/kg to about 100 mg/kg per day. This includes 0.001, 0.0025,0.005, 0.0075, 0.01, 0.025, 0.05, 0.075, 0.1, 0.25, 0.5, 0.75, 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70,75, 80, 85, 90, 95, or 100 mg/kg.

Generally, a therapeutically effective amount of the compound of Formula1, or a stereoisomer thereof, or a pharmaceutically acceptable saltthereof, will range from a total daily dosage of about 0.1 mg/day to1000 mg/day, about 30-720 mg/day, about 60-600 mg/day, or about 100-480mg/day, or more. In some embodiments, a therapeutically effective amountof the compound of Formula 1, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof, will range from about 1-240mg/day, about 30-240 mg/day, about 30-200 mg/day, about 30-120 mg/day,about 1-120 mg/day, about 50-150 mg/day, about 60-150 mg/day, about60-120 mg/day, or about 60-100 mg/day, administered as either a singledosage or as multiple dosages. In some embodiments, multiple dosagesinclude two, three, or four doses per day.

In some embodiments, the therapeutically effective amount of thecompound of Formula 1, or a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof, is at least 0.1 mg/day, at least 0.5 mg/day, atleast 1 mg/day, at least 5 mg/day, at least 10 mg/day, at least 20mg/day, at least 30 mg/day, at least 40 mg/day, at least 50 mg/day, atleast 60 mg/day, at least 70 mg/day, at least 80 mg/day, at least 90mg/day, at least 100 mg/day, at least 110 mg/day, at least 120 mg/day,at least 130 mg/day, at least 140 mg/day, at least 150 mg/day, at least160 mg/day, at least 170 mg/day, at least 180 mg/day, at least 190mg/day, at least 200 mg/day, at least 225 mg/day, at least 250 mg/day,at least 275 mg/day, at least 300 mg/day, at least 325 mg/day, at least350 mg/day, at least 375 mg/day, at least 400 mg/day, at least 425mg/day, at least 450 mg/day, at least 475 mg/day, at least 500 mg/day,at least 525 mg/day, at least 550 mg/day, at least 575 mg/day, at least600 mg/day, at least 625 mg/day, at least 650 mg/day, at least 675mg/day, at least 700 mg/day, at least 725 mg/day, at least 750 mg/day,at least 775 mg/day, at least 800 mg/day, at least 825 mg/day, at least850 mg/day, at least 875 mg/day, at least 900 mg/day, at least 925mg/day, at least 950 mg/day, at least 975 mg/day, or at least 1000mg/day.

Of course, the dosage may be changed according to the patient's age,weight, susceptibility, symptom, or the efficacy of the compound.

In some embodiments, the present technology provides a method ofinhibiting vascular adhesion protein (VAP)-1 in a mammal, comprisingadministering to the mammal a therapeutically effective amount of acompound of Formula 1, or a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof. In one embodiment, the present technologyprovides a method for treating nonalcoholic hepatosteatosis (NASH),comprising administering to a mammal a therapeutically effective amountof a compound of Formula 1, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof. In some embodiments, providedherein is a method for treating NASH in a subject in need thereof, themethod comprising, consisting essentially of, or consisting ofadministering to the subject a therapeutically effective amount of acompound of Formula 1, or a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof. Mammals include, but are not limited to, mice,rodents, rats, simians, humans, farm animals, dogs, cats, sport animals,and pets.

In some embodiments, the present technology provides a use of thecompound of Formula 1 above, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof for use in the preparation of amedicament for inhibiting a vascular adhesion protein-1 (VAP-1) inmammals.

In one embodiment, the present technology provides a use of the compoundof Formula 1 above, or a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof for use in the preparation of a medicament fortreating or preventing nonalcoholic hepatosteatosis (NASH).

Hereinafter, the present technology is further elaborated throughexamples and experimental examples. However, the following examples andexperimental examples are provided for illustration purposes only, andare not intended to limit the scope of the invention.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presenttechnology. Any recited method can be carried out in the order of eventsrecited or in any other order which is logically possible.

EXAMPLES

The analyses of the compounds prepared in the following examples werecarried out as follows: Nuclear magnetic resonance (NMR) spectrumanalysis was carried out using Bruker 400 MHz spectrometer and Agilent600 MHz spectrometer and chemical shifts thereof were analyzed in ppm.Further, the indicated molecular weights were measured by using liquidchromatography/mass selective detector (MSD) of Agilent 1260 Infinityseries equipped with an electrostatic spray interface (by using SingleQuadrupole, it indicates a value of m/z in ESI+ (ESI-MS (cation), whichis represented by the [M+H]+peak). Column chromatography was carried outon silica gel (Merck, 70-230 mesh). (W. C. Still, J. Org. Chem., 43,2923, 1978). Further, the abbreviations used in the following examplesare as follows: ‘methyl’ is abbreviated to ‘Me’; ‘ethyl’ is abbreviatedto ‘Et’; ‘phenyl’ is abbreviated to ‘Ph, tert-butyloxycarbonyl isabbreviated to ‘Boc’; and tert-butyl dimethylsilyl is abbreviated toTBDMS. Further, the starting materials in each Example are knowncompounds, which were synthesized according literatures or obtained fromSigma-Aldrich.

Reference Example 1. tert-butylN-[3,3-difluoro-2-(hydroxymethyl)allyl]carbamate Step 1: tert-butylN-[2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,3-difluoro-allyl]carbamate

Under nitrogen condition, 2.4 g of tert-butylN-[3-[tert-butyl(dimethyl)silyl]oxy-2-oxo-propyl]carbamate and 1.0 g of2-(difluoromethylsulfonyl)pyridine were dissolved in 34.5 mL ofN,N-dimethylformamide and then cooled to −70° C. To the reactionmixture, 10.4 mL of a tetrahydrofuran solution of 1.0 M lithiumbis(trimethylsilyl)amide was slowly added dropwise. The resultingsolution was stirred at −70° C. for 30 minutes and then stirred again byslowly increasing the temperature to −10° C. 20 mL of an ammoniumchloride solution was added to the reaction mixture, followed by theaddition of 20 mL of a 3 N hydrogen chloride solution. The reactionmixture was extracted with ethyl acetate three times. The extractedorganic layer was washed with brine, dried over anhydrous magnesiumsulfate, and concentrated under reduced pressure to give a yellow liquidresidue. The residue was purified with silica gel column chromatography(developing solvent: n-hexane/ethyl acetate=20/1) to give 446.0 mg ofthe title compound as a yellow liquid (yield: 25.5%). ¹H-NMR (CDCl₃, 400MHz) δ 4.98 (s, 1H), 4.20 (s, 2H), 3.83 (s, 2H), 1.42 (s, 9H), 0.89 (s,9H), 0.07 (s, 6H)

Step 2: tert-butyl N-[3,3-difluoro-2-(hydroxymethyl)allyl]carbamate

426 mg of tert-butylN-[2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,3-difluoro-allyl]carbamatewas dissolved in 2.0 mL of tetrahydrofuran, followed by the addition of1.5 mL of a tetrahydrofuran solution of 1.0 M tetrabutylamoniumfluoride(TBAF), and then the resulting solution was stirred at room temperaturefor 2 hours. Ethyl acetate and water were added to the reaction mixtureto separate an organic layer. Ethyl acetate was added to the aqueouslayer of the reaction mixture to separate an organic layer again. Theorganic layers thus obtained were combined and washed with an ammoniumchloride solution and brine, dried over anhydrous magnesium sulfate, andconcentrated under reduced pressure to give a yellow residue. Theresidue was purified with silica gel column chromatography (developingsolvent: n-hexane/ethyl acetate=2/1) to give 285 mg of the titlecompound as a colorless liquid (yield: 100%). ¹H-NMR (CDCl₃, 400 MHz) δ4.91 (s, 1H), 4.14 (s, 2H), 3.86 (d, 2H), 3.72 (s, 1H), 1.45 (s, 9H)

Reference Example 2. 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one Step 1:(E)-ethyl 2-(ethoxymethylene)hydrazinecarboxylate

30.0 g of ethyl carbazate was dissolved in 240.2 mL of triethylorthoformate and then stirred overnight at 110° C. The reaction mixturewas cooled to room temperature and concentrated under reduced pressureto give 30.3 g of the title compound as a white solid (yield: 65.6%).¹H-NMR (DMSO-d₆, 400 MHz) δ 10.09 (s, 1H), 7.94 (s, 1H), 4.03 (t, 4H),1.24-1.16 (m, 6H)

Step 2: 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one

4.3 g of (E)-ethyl 2-(ethoxymethylene)hydrazinecarboxylate prepared inStep 1 was dissolved in 90 mL of methanol, 3.0 g of 4-fluoroaniline wasadded thereto, and then the resulting solution was stirred at 80° C. for5 hours. After the reaction mixture was cooled to room temperature, 7.7mL of a sodium methoxide solution (<25% in methanol>) was added thereto.The resulting solution was refluxed overnight at 80° C. The reactionmixture was cooled to room temperature and concentrated under reducedpressure. Ethyl acetate was added to the resultant residue and thenwashed with an ammonium chloride solution. The organic layer thereof wasdried over anhydrous magnesium sulfate and concentrated under reducedpressure to give 948 mg of the title compound as a light grey solid(yield: 19.6%). MS (ESI) m/z=180.1 (M+H)+

Reference Example 3. 4-(3-bromophenyl)-1H-1,2,4-triazol-5-one Step 1:phenyl (3-bromophenyl)carbamate

1.0 g of 3-bromoaniline and 0.98 mL of pyridine were dissolved in 10.0mL of ethyl acetate. To the resulting solution, 0.77 mL ofphenylchloroformate at 0° C. was slowly added, and the solution wasstirred at room temperature for 3 hours. To the solution, ethyl acetatewas added, and the resulting reaction mixture was washed with 1Nhydrochloric acid solution and brine, dried over anhydrous magnesiumsulfate, and concentrated under reduced pressure to give 1.4 g of thetitle compound as a yellow solid (yield: 80.80%).

Step 2: N-(3-bromophenyl)hydrazine carboxamide

1.4 g of phenyl (3-bromophenyl)carbamate prepared in Step 1 and 480.0 mgof hydrazine hydrate were dissolved in 4.0 mL of tetrahydrofuran and 4.0mL of ethanol, and the resulting solution was stirred overnight at roomtemperature. The resulting reaction mixture was concentrated and thenwashed with ethyl acetate to give 890.0 mg of the title compound as awhite solid (yield: 80.0%).

Step 3: 4-(3-bromophenyl)-1H-1,2,4-triazol-5-one

890.0 mg of N-(3-bromophenyl)hydrazine carboxamide prepared in Step 2and 1.6 g of formamidine acetate were dissolved in 8.9 mL of 1-propanol,and the resulting solution was stirred at room temperature for 30minutes, and then 1.3 mL of acetic acid was added and stirred at 80° C.for 8 hours. The reaction mixture was cooled to room temperature,distilled water was added to the cooled reaction mixture, and then thereaction mixture was stirred overnight. The resulting crystals werefiltered and dried to give 742.8 mg of the title compound as a whitesolid (yield: 80.2%). MS (ESI) m/z=241.2 (M+H)+

Reference Example 4. 4-(3,4-difluorophenyl)-1H-1,2,4-triazol-5-one

492.0 mg of the title compound (yield: 32.2%) was prepared in the samefashion as Reference Example 2, except that 1.0 g of 3,4-difluoroanilinewas used in Step 2 instead of 4-fluoroaniline. ¹H-NMR (MeOD, 400 MHz) δ8.16 (s, 1H), 7.73 (t, 1H), 7.47-7.42 (m, 2H)

Reference Example 5. 4-(4-bromo-3-fluorophenyl)-1H-1,2,4-triazol-5-one

517.3 mg of the title compound (yield: 38.1%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of4-bromo-3-fluoroaniline was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=259.1 (M+H)+

Reference Example 6. 4-(4-bromo-2-fluorophenyl)-1H-1,2,4-triazol-5-one

443.5 mg of the title compound (yield: 32.7%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of4-bromo-2-fluoroaniline was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=259.2 (M+H)+

Reference Example 7. 4-(4-bromo-2-methylphenyl)-1H-1,2,4-triazol-5-one

450 mg of the title compound (yield: 33.0%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of4-bromo-3-methylaniline was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=255.1 (M+H)+

Reference Example 8. 4-(6-bromo-3-pyridyl)-1H-1,2,4-triazol-5-one

500.7 mg of the title compound (yield: 35.9%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of3-amino-6-bromopyridine was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=242.1 (M+H)+

Reference Example 9. 4-(6-bromo-2-pyridyl)-1H-1,2,4-triazol-5-one

6.0 g of the title compound (yield: 86.1%) was prepared in the samefashion as Reference Example 3, except that 5.0 g of2-amino-6-bromopyridine was used in Step 1 instead of 3-bromoaniline.¹H-NMR (CDCl₃, 400 MHz) δ 9.79 (s, 1H), 8.44 (s, 1H), 8.33 (d, 1H), 7.71(t, 1H), 7.43 (d, 1H)

Reference Example 10. 4-(4-bromo-2-pyridyl)-1H-1,2,4-triazol-5-one

902.2 mg of the title compound (yield: 64.8%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of2-amino-4-bromopyridine was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=242.1 (M+H)+

Reference Example 11. 4-(2-bromo-4-pyridyl)-1H-1,2,4-triazol-5-one

2.0 g of the title compound (yield: 28.7%) was prepared in the samefashion as Reference Example 3, except that 5.0 g of4-amino-2-bromopyridine was used in Step 1 instead of 3-bromoaniline.¹H-NMR (DMSO-d₆, 600 MHz) δ 8.65 (s, 1H), 8.45 (d, 1H), 8.17 (s, 1H),8.12 (d, 1H), 7.97 (dd, 1H)

Reference Example 12.4-(5-bromo-3-methyl-2-pyridyl)-1H-1,2,4-triazol-5-one

1.9 g of the title compound (yield: 69.6%) was prepared in the samefashion as Reference Example 3, except that 2.0 g of2-amino-5-bromo-3-methylpyridine was used in Step 1 instead of3-bromoaniline. ¹H-NMR (DMSO-d₆, 400 MHz) δ 8.55 (d, 1H), 8.21 (s, 1H),8.13 (s, 1H), 2.27 (s, 3H)

Reference Example 13.4-(6-bromo-4-methyl-3-pyridyl)-1H-1,2,4-triazol-5-one

4.5 g of the title compound (yield: 66.1, %) was prepared in the samefashion as Reference Example 3, except that 5.0 g of2-bromo-4-methyl-5-aminopyridine was used in Step 1 instead of3-bromoaniline. MS (ESI) m/z=256.0 (M+H)+

Reference Example 14.4-(6-bromo-5-methyl-3-pyridyl)-1H-1,2,4-triazol-5-one

362.1 mg of the title compound (yield: 26.5%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of5-amino-2-bromo-3-picoline was used in Step 1 instead of 3-bromoaniline.MS (ESI) m/z=256.1 (M+H)+

Reference Example 15.4-(5-bromo-3-fluoro-2-pyridyl)-1H-1,2,4-triazol-5-one

715.0 mg of the title compound (yield: 52.7%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of2-amino-5-bromo-3-fluoropyridine was used in Step 1 instead of3-bromoaniline. MS (ESI) m/z=260.2 (M+H)+

Reference Example 16.4-(6-bromo-3-methyl-2-pyridyl)-1H-1,2,4-triazol-5-one

1.8 g of the title compound (yield: 65.9%) was prepared in the samefashion as Reference Example 3, except that 2.0 g of2-amino-6-bromo-3-methylpyridine was used in Step 1 instead of3-bromoaniline. MS (ESI) m/z=256.1 (M+H)+

Reference Example 17. 4-(5-bromopyrazin-2-yl)-1H-1,2,4-triazol-5-one

4.3 g of the title compound (yield: 61.9%) was prepared in the samefashion as Reference Example 3, except that 5.0 g of2-amino-5-bromopyrazine was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=243.2 (M+H)+

Reference Example 18.4-[(4-benzyloxyphenyl)methyl]-1H-1,2,4-triazol-5-one

570 mg of the title compound (yield: 43.2%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of(4-(benzyloxy)phenyl)methylamine was used in Step 1 instead of3-bromoaniline. MS (ESI) m/z=282.2 (M+H)+

Reference Example 19.4-[(5-bromo-2-thienyl)methyl]-1H-1,2,4-triazol-5-one

742.8 mg of the white solid title compound (yield: 80.3%) was preparedin the same fashion as Reference Example 2, except that 1.0 g of(5-bromothiophen-2-yl)methylamine was used in Step 2 instead of4-fluoroaniline. ¹H-NMR (MeOD, 400 MHz) δ 7.83 (s, 1H), 7.01 (s, 1H),6.94 (s, 1H), 5.04 (s, 2H).

Reference Example 20.4-[(4-bromo-2-thienyl)methyl]-1H-1,2,4-triazol-5-one

3.9 g of the title compound (yield: 57.6%) was prepared in the samefashion as Reference Example 2, except that 5.0 g of(4-bromothiophen-2-yl)methylamine was used in Step 2 instead of4-fluoroaniline. ¹H-NMR (DMSO-d₆, 400 MHz) δ 11.74 (s, 1H), 7.97 (s,1H), 7.61 (s, 1H), 7.10 (s, 1H), 4.92 (s, 2H)

Reference Example 21.4-[(5-bromo-3-methyl-2-thienyl)methyl]-1H-1,2,4-triazol-5-one

1.4 g of the title compound (yield: 41.2%) was prepared in the samefashion as Reference Example 3, except that 2.6 g of(5-bromo-3-methylthiophen-2-yl)methylamine was used in Step 1 instead of3-bromoaniline. MS (ESI) m/z=275.1 (M+H)+

Reference Example 22. 4-[2-(2-thienyl)ethyl]-1H-1,2,4-triazol-5-one

569 mg of the white solid title compound (yield: 72.0%) was prepared inthe same fashion as Reference Example 3, except that 1.0 g of2-thiophenethylamine was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=196.2 (M+H)+

Reference Example 23.4-[2-(5-bromo-2-thienyl)ethyl]-1H-1,2,4-triazol-5-one

2.1 g of the title compound (yield: 68.6%) was prepared in the samefashion as Reference Example 2, except that 2.3 g of2-(5-bromothiophen-2-yl)ethan-1-amine was used in Step 2 instead of4-fluoroaniline. MS (ESI) m/z=275.2 (M+H)+

Reference Example 24. tert-butylN-[3,3-difluoro-2-[[4-(4-fluorophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamate

321 mg of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one prepared in Step 2of Reference Example 2, 400 mg of tert-butylN-[3,3-difluoro-2-(hydroxymethyl)allyl]carbamate prepared in Step 2 ofReference Example 1, and 940 mg of triphenylphosphine were dissolved in4.5 mL of tetrahydrofuran, and the resulting solution was stirred andcooled to 0° C. To the reaction mixture, 706 uL of diisopropylazodicarboxylate (DIAD) was slowly added dropwise and stirred at roomtemperature for 6 hours. The reaction mixture was concentrated underreduced pressure to give a yellow liquid residue. The residue waspurified with silica gel column chromatography (developing solvent:n-hexane/ethyl acetate=2/1) to give 222 mg of the title compound as acolorless liquid (yield: 32.3%). ¹H-NMR (CDCl₃, 400 MHz) δ 7.68 (s, 1H),7.52 (s, 2H), 7.19 (t, 2H), 5.37 (s, 1H), 4.54 (s, 2H), 3.79 (s, 2H),1.41 (s, 9H)

Reference Example 25. tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

30 mg of the title compound (yield: 10.0%) was prepared in the samefashion as Reference Example 24, except that 161 mg of4-(3-bromophenyl)-1H-1,2,4-triazol-5-one prepared in Reference Example 3was used instead of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI)m/z=346.2 (M+H)+

Reference Example 26. tert-butylN-[2-[[4-(3,4-difluorophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

1.8 g of the title compound (yield: 100%) was prepared in the samefashion as Reference Example 24, except that 883 mg of4-(3,4-difluorophenyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 4 was used instead of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one.MS (ESI) m/z=303.1 (M+H)+

Reference Example 27. tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

19 mg of the title compound (yield: 9.3%) was prepared in the samefashion as Reference Example 24, except that 150 mg of4-(4-bromo-3-fluorophenyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 5 was used instead of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one.MS (ESI) m/z=(M+H)+

Reference Example 28. tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

448 mg of the title compound (yield: 8.3%) was prepared in the samefashion as Reference Example 24, except that 3.0 g of4-(4-bromo-2-fluorophenyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 6 was used instead of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one.MS (ESI) m/z=364.2 (M+H)+

Reference Example 29. tert-butylN-[2-[[4-(4-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

35 mg of the title compound (yield: 24.2%) was prepared in the samefashion as Reference Example 24, except that 80 mg of4-(4-bromo-2-methylphenyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 7 was used instead of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one.MS (ESI) m/z=360.1 (M+H)+

Reference Example 30. tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

1.3 g of the title compound (yield: 41.3%) was prepared in the samefashion as Reference Example 24, except that 1.7 g of4-(6-bromo-3-pyridyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 8 was used instead of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one.MS (ESI) m/z=347.2 (M+H)+

Reference Example 31. tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

1.8 g of the title compound (yield: 100%) was prepared in the samefashion as Reference Example 24, except that 972 mg of4-(6-bromo-2-pyridyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 9 was used instead of 4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one.¹H-NMR (CDCl₃, 400 MHz) δ 8.42 (s, 1H), 8.32 (d, 1H), 7.70 (t, 1H), 7.43(d, 1H), 4.53 (s, 2H), 3.78 (s, 2H), 1.40 (s, 9H)

Reference Example 32. tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

499 mg of the title compound (yield: 49.9%) was prepared in the samefashion as Reference Example 24, except that 540 mg of4-(4-bromo-2-pyridyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 10 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=347.2 (M+H)+

Reference Example 33. tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

1.2 g of the title compound (yield: 90.0%) was prepared in the samefashion as Reference Example 24, except that 702 mg of4-(2-bromo-4-pyridyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 11 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=347.1 (M+H)+

Reference Example 34. tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

1.8 g of the title compound (yield: 97.0%) was prepared in the samefashion as Reference Example 24, except that 1.0 g of4-(5-bromo-3-methyl-2-pyridyl)-1H-1,2,4-triazol-5-one prepared inReference Example 12 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ8.42 (s, 1H), 7.87 (s, 1H), 7.74 (s, 1H), 5.36 (s, 1H), 4.53 (s, 2H),3.78 (s, 2H), 2.40 (s, 3H), 1.42 (s, 9H)

Reference Example 35. tert-butylN-[2-[[4-(6-bromo-4-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

56 mg of the title compound (yield: 34.4%) was prepared in the samefashion as Reference Example 24, except that 89 mg of4-(6-bromo-4-methyl-3-pyridyl)-1H-1,2,4-triazol-5-one prepared inReference Example 13 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=361.1 (M+H)+

Reference Example 36. tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

405 mg of the title compound (yield: 39.3%) was prepared in the samefashion as Reference Example 24, except that 571 mg of4-(6-bromo-5-methyl-3-pyridyl)-1H-1,2,4-triazol-5-one prepared inReference Example 14 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=361.1 (M+H)+

Reference Example 37. tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

780 mg of the title compound (yield: 33.5%) was prepared in the samefashion as Reference Example 24, except that 1.3 g of4-(5-bromo-3-fluoro-2-pyridyl)-1H-1,2,4-triazol-5-one prepared inReference Example 15 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=365.2 (M+H)+

Reference Example 38. tert-butylN-[2-[[4-(6-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

521 mg of the title compound (yield: 50.5%) was prepared in the samefashion as Reference Example 24, except that 571 mg of4-(6-bromo-3-methyl-2-pyridyl)-1H-1,2,4-triazol-5-one prepared inReference Example 14 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=361.2 (M+H)+

Reference Example 39. tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

110 mg of the title compound (yield: 43.1%) was prepared in the samefashion as Reference Example 24, except that 138 mg of4-(5-bromopyrazin-2-yl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 17 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=348.1 (M+H)+

Reference Example 40. tert-butylN-[2-[[4-[(4-benzyloxyphenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

20 mg of the title compound (yield: 4.6%) was prepared in the samefashion as Reference Example 24, except that 126 mg of4-[(4-benzyloxyphenyl)methyl]-1H-1,2,4-triazol-5-one prepared inReference Example 18 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=387.1 (M+H)+

Reference Example 41. tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

3.3 g of the title compound (yield: 87.2%) was prepared in the samefashion as Reference Example 24, except that 2.0 g of4-[(5-bromo-2-thienyl)methyl]-1H-1,2,4-triazol-5-one prepared inReference Example 19 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ7.38 (s, 1H), 6.95 (s, 1H), 6.85 (s, 1H), 5.40 (s, 1H), 4.88 (s, 2H),4.47 (s, 2H), 3.71 (s, 2H), 1.44 (s, 9H)

Reference Example 42. tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

2.9 g of the title compound (yield: 64.9%) was prepared in the samefashion as Reference Example 24, except that 2.3 g of4-[(4-bromo-2-thienyl)methyl]-1H-1,2,4-triazol-5-one prepared inReference Example 20 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ7.41 (s, 1H), 7.22 (s, 1H), 7.02 (s, 1H), 5.38 (s, 1H), 4.93 (s, 2H),4.48 (s, 2H), 3.72 (s, 2H), 1.44 (s, 9H)

Reference Example 43. tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

546 mg of the title compound (yield: 33.0%) was prepared in the samefashion as Reference Example 24, except that 946 mg of4-[(5-bromo-3-methyl-2-thienyl)methyl]-1H-1,2,4-triazol-5-one preparedin Reference Example 21 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=380.2 (M+H)+

Reference Example 44. tert-butylN-[3,3-difluoro-2-[[5-oxo-4-[2-(2-thienyl)ethyl]-1,2,4-triazol-1-yl]methyl]allyl]carbamate

44 mg of the title compound (yield: 14.3%) was prepared in the samefashion as Reference Example 24, except that 87 mg of4-[2-(2-thienyl)ethyl]-1H-1,2,4-triazol-5-one prepared in ReferenceExample 22 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=387.2 (M+H)+

Reference Example 45. tert-butylN-[2-[[4-(5-bromo-2-thienyl)ethyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

780 mg of the title compound (yield: 22.3%) was prepared in the samefashion as Reference Example 24, except that 2.0 g of4-[2-(5-bromo-2-thienyl)ethyl]-1H-1,2,4-triazol-5-one prepared inReference Example 23 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=380.1 (M+H)+

Reference Example 46. 4-(3-bromo-2-methyl-phenyl)-1H-1,2,4-triazol-5-one

528 mg of the title compound (yield: 38.7%) was prepared in the samefashion as Reference Example 3, except that 1.0 g of3-bromo-2-methylaniline was used in Step 1 instead of 3-bromoaniline. MS(ESI) m/z=255.2 (M+H)+

Reference Example 47. 4-[(4-bromophenyl)methyl]-1H-1,2,4-triazol-5-one

1.0 g of 1,4-dihydro-1,2,4-triazol-5-one and 3.2 g of potassiumcarbonate were dissolved in 100.0 mL of N,N-dimethylformamide, and thesolution was stirred at RT for 10 min. 2.9 g of 4-bromobenzyl bromidewas added to the resulting solution, and then the solution was stirredat RT for 16 hours. After addition of distilled water, the reactionmixture was extracted with ethyl acetate three times. The combinedorganic extracts were dried over anhydrous magnesium sulfate and thenconcentrated under reduced pressure to give a residue as a yellowliquid. The residue was purified with silica gel column chromatography(developing solvent: n-hexane/ethyl acetate=1/2) to give 715 mg of thetitle compound as a white solid (yield: 23.9%). ¹H-NMR (DMSO-d₆, 400MHz) δ 11.7 (s, 1H), 7.96 (s, 1H), 7.56 (d, 2H), 7.24 (d, 2H), 4.73 (s,2H)

Reference Example 48. 4-[(3-bromophenyl)methyl]-1H-1,2,4-triazol-5-one

944 mg of the title compound (yield: 31.6%) was prepared as a whitesolid in the same fashion as Reference Example 47, except that 2.9 g of3-bromobenzyl bromide was used instead of 4-bromobenzyl bromide. ¹H-NMR(DMSO-d₆, 400 MHz) δ 11.8 (s, 1H), 8.00 (s, 1H), 7.51 (d, 2H), 7.35-7.28(m, 2H), 4.76 (s, 2H)

Reference Example 49. 4-[(2-bromophenyl)methyl]-1H-1,2,4-triazol-5-one

1.4 g of the title compound (yield: 48.4%) was prepared as a white solidin the same fashion as Reference Example 47, except that 2.9 g of2-bromobenzyl bromide was used instead of 4-bromobenzyl bromide. ¹H-NMR(DMSO-d₆, 400 MHz) δ 11.80 (s, 1H), 7.91 (s, 1H), 7.67 (d, 1H), 7.40 (t,1H), 7.28 (t, 1H), 7.09 (d, 1H), 4.81 (s, 2H)

Reference Example 50.4-[(6-bromobenzothiophen-2-yl)methyl]-1H-1,2,4-triazol-5-one

1.5 g of the title compound (yield: 66.8%) was prepared as a pale pinksolid in the same fashion as Reference Example 2, except that 1.8 g of(6-bromo-1-benzothiophen-2-yl)methanamine was used in Step 2 instead of4-fluoroaniline. MS (ESI) m/z=311.2 (M+H)+

Reference Example 51.4-[(5-bromobenzothiophen-2-yl)methyl]-1H-1,2,4-triazol-5-one

1.5 g of the title compound (yield: 57.5%) was prepared as a pale brownsolid in the same fashion as Reference Example 2, except that 2.0 g of(5-bromo-1-benzothiophen-2-yl)methanamine was used in Step 2 instead of4-fluoroaniline. ¹H-NMR (DMSO-d₆, 400 MHz) δ 11.8 (s, 1H), 8.24 (s, 1H),8.00 (s, 1H), 7.78 (d, 1H), 7.52 (d, 1H), 7.36 (s, 1H), 5.04 (s, 2H)

Reference Example 52.4-[(5-bromo-3-fluoro-2-thienyl)methyl]-1H-1,2,4-triazol-5-one

689 mg of the title compound (yield: 66.0%) was prepared as a paleyellow liquid in the same fashion as Reference Example 47, except that1.1 g of (5-bromo-3-fluoro-2-thienyl)methyl methanesulfonate was usedinstead of 4-bromobenzyl bromide. ¹H-NMR (MeOD, 400 MHz) δ 7.84 (s, 1H),7.02 (s, 1H), 4.93 (s, 2H)

Reference Example 53. tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

4.7 g of the title compound (yield: 86.1%) was prepared in the samefashion as Reference Example 24, except that 3.0 g of4-(3-bromo-2-methyl-phenyl)-1H-1,2,4-triazol-5-one prepared in ReferenceExample 46 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ7.70 (d, 1H), 7.49 (s, 1H), 7.24-7.18 (m, 2H), 5.41 (bs, 1H), 4.57 (s,2H), 3.81 (d, 2H), 2.33 (s, 3H), 1.44 (s, 9H)

Reference Example 54. tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

624 mg of the title compound (yield: 48.3%) was prepared in the samefashion as Reference Example 24, except that 715 mg of4-[(4-bromophenyl)methyl]-1H-1,2,4-triazol-5-one prepared in ReferenceExample 47 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ7.60 (s, 1H), 7.55 (d, 2H), 7.43 (d, 2H), 5.18 (s, 2H), 4.66 (s, 2H),4.37 (s, 2H), 1.33 (s, 9H)

Reference Example 55. tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

790 mg of the title compound (yield: 64.0%) was prepared in the samefashion as Reference Example 24, except that 683 mg of4-[(3-bromophenyl)methyl]-1H-1,2,4-triazol-5-one prepared in ReferenceExample 48 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=459.1 (M+H)+

Reference Example 56. tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

692 mg of the title compound (yield: 56.2%) was prepared in the samefashion as Reference Example 24, except that 683 mg of4-[(2-bromophenyl)methyl]-1H-1,2,4-triazol-5-one prepared in ReferenceExample 49 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. MS (ESI) m/z=460.1 (M+H)+

Reference Example 57. tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

368 mg of the title compound (yield: 37.0%) was prepared in the samefashion as Reference Example 24, except that 600 mg of4-[(6-bromobenzothiophen-2-yl)methyl]-1H-1,2,4-triazol-5-one prepared inReference Example 50 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ7.92 (s, 1H), 7.60 (d, 1H), 7.48-7.43 (m, 2H), 7.26 (s, 1H), 5.34 (s,1H), 5.02 (s, 2H), 4.48 (s, 2H), 3.73 (s, 2H), 1.42 (s, 9H)

Reference Example 58. tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

344 mg of the title compound (yield: 44.5%) was prepared in the samefashion as Reference Example 24, except that 464 mg of4-[(5-bromobenzothiophen-2-yl)methyl]-1H-1,2,4-triazol-5-one prepared inReference Example 51 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ7.91 (s, 1H), 7.66 (d, 1H), 7.46 (d, 2H), 7.28 (s, 1H), 5.41 (bs, 1H),5.06 (s, 2H), 4.51 (s, 2H), 3.75 (s, 2H), 1.45 (s, 9H)

Reference Example 59. tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

581 mg of the title compound (yield: 48.6%) was prepared as a yellowliquid in the same fashion as Reference Example 24, except that 689 mgof 4-[(5-bromo-3-fluoro-2-thienyl)methyl]-1H-1,2,4-triazol-5-oneprepared in Reference Example 52 was used instead of4-(4-fluorophenyl)-1H-1,2,4-triazol-5-one. ¹H-NMR (CDCl₃, 400 MHz) δ7.44 (s, 1H), 6.85 (s, 1H), 6.37 (s, 1H), 4.83 (s, 2H), 4.47 (s, 2H),3.73 (s, 2H), 1.45 (s, 9H)

Example 1.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazol-3-onetrifluoroacetate

287 mg of tert-butylN-[3,3-difluoro-2-[[4-(4-fluorophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamateprepared in Reference Example 24 was dissolved in 10.0 mL ofdichloromethane and 1.1 mL of trifluoroacetic acid was added thereto.The resulting solution was stirred at room temperature for 2.5 hours.The reaction mixture thus obtained was concentrated, followed by theaddition of dichloromethane. The solution was concentrated under reducedpressure and then dried in vacuo to obtain a yellow liquid residue. Theresidue was purified with silica gel column chromatography (developingsolvent: dichloromethane/methanol=10/1) to give 262 mg of the titlecompound as a white solid (yield: 100%). ¹H-NMR (MeOD, 400 MHz) δ 8.23(s, 1H), 7.65 (s, 2H), 7.27 (t, 2H), 4.64 (s, 2H), 3.73 (s, 2H).

Example 2.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3-bromophenyl)-1,2,4-triazol-3-onetrifluoroacetate

31 mg of the title compound (yield: 40.1%) was prepared in the samefashion as Example 1, except that 96 mg of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.30(s, 1H), 7.95 (s, 1H), 7.65-7.56 (m, 2H), 7.44 (t, 1H), 4.63 (s, 2H),3.72 (s, 2H)

Example 3.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3,4-difluorophenyl)-1,2,4-triazol-3-onetrifluoroacetate

143 mg of the title compound as a colorless liquid (yield: 100%) wasprepared in the same fashion as Example 1, except that 189 mg oftert-butylN-[2-[[4-(3,4-difluorophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 26 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.29(s, 1H), 7.74 (t, 3H), 7.48 (s, 1H), 7.42 (t, 1H), 4.65 (s, 2H), 3.75(s, 2H)

Example 4.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-3-fluoro-phenyl)-1,2,4-triazol-3-onetrifluoroacetate

56 mg of the title compound (yield: 58.0%) was prepared in the samefashion as Example 1, except that 123 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.34(s, 1H), 7.79-7.69 (m, 2H), 7.47 (d, 2H), 4.63 (s, 2H), 3.72 (s, 2H)

Example 5.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazol-3-onetrifluoroacetate

51 mg of the title compound (yield: 57.7%) was prepared in the samefashion as Example 1, except that 113 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.11(s, 1H), 7.65-7.53 (m, 3H), 4.64 (s, 2H), 3.73 (s, 2H)

Example 6.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-methyl-phenyl)-1,2,4-triazol-3-onetrifluoroacetate

27 mg of the title compound (yield: 69.0%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(4-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 29 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.02(s, 1H), 7.58-7.55 (m, 2H), 7.34 (d, 2H), 4.64 (s, 2H), 3.73 (s, 2H),2.20 (s, 3H)

Example 7.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

34 mg of the title compound (yield: 87.7%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.73(s, 1H), 8.35 (s, 1H), 8.06 (d, 1H), 7.76 (d, 1H), 5.49 (s, 2H), 4.62(s, 2H), 3.54 (s, 2H)

Example 8.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-2-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

325 mg of the title compound (yield: 98.4%) was prepared in the samefashion as Example 1, except that 369 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.58(s, 1H), 8.26 (d, 1H), 7.87 (t, 1H), 7.58 (d, 1H), 4.65 (s, 2H), 3.74(s, 2H)

Example 9.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

38 mg of the title compound (yield: 98.0%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.62(s, 1H), 8.48 (s, 1H), 8.32 (d, 1H), 7.56 (d, 1H), 4.66 (s, 2H), 3.75(s, 2H)

Example 10.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(2-bromo-4-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

34 mg of the title compound (yield: 88.4%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.69(s, 1H), 8.44 (d, 2H), 8.21 (s, 1H), 7.89 (d, 1H), 4.65 (s, 2H), 3.73(s, 2H)

Example 11.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-methyl-2-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

260 mg of the title compound (yield: 73.0%) was prepared in the samefashion as Example 1, except that 455 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.50(s, 1H), 8.13 (s, 2H), 4.64 (s, 2H), 3.73 (s, 2H), 2.34 (s, 3H)

Example 12.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-4-methyl-3-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 89.2%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(6-bromo-4-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 35 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.31(s, 1H), 8.08 (s, 1H), 7.72 (s, 1H), 4.65 (s, 2H), 3.74 (s, 2H), 2.29(s, 3H)

Example 13.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-5-methyl-3-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

22 mg of the title compound (yield: 56.0%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 36 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.57(s, 1H), 8.35 (s, 1H), 8.06 (d, 1H), 4.64 (s, 2H), 3.67 (s, 2H), 2.46(s, 3H)

Example 14.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-fluoro-2-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

19 mg of the title compound (yield: 48.3%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.54(s, 1H), 8.24 (d, 1H), 8.20 (s, 1H), 4.65 (s, 2H), 3.74 (s, 2H)

Example 15.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-methyl-2-pyridyl)-1,2,4-triazol-3-onetrifluoroacetate

28 mg of the title compound (yield: 71.3%) was prepared in the samefashion as Example 1, except that 50 mg of tert-butylN-[2-[[4-(6-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 38 was used. ¹H-NMR (MeOD, 400 MHz) δ 8.15(s, 1H), 7.79 (d, 1H), 7.66 (d, 1H), 4.65 (s, 2H), 3.72 (s, 2H), 2.31(s, 3H)

Example 16.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromopyrazin-2-yl)-1,2,4-triazol-3-onetrifluoroacetate

56 mg of the title compound (yield: 65.6%) was prepared in the samefashion as Example 1, except that 110 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used. ¹H-NMR (MeOD, 400 MHz) δ 9.31(s, 1H), 8.67 (s, 1H), 8.58 (s, 1H), 4.65 (s, 2H), 3.73 (s, 2H)

Example 17.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-onetrifluoroacetate Step 1: tert-butylN-[3,3-difluoro-2-[[4-[3-(4-methylsulfonylphenyl)phenyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamate

70 mg of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 31 mg of4-(methanesulfonyl)phenylboronic acid were dissolved in 1.0 mL of1,4-dioxane, followed by the addition of 785 uL of 1 M potassiumcarbonate and 6 mg ofpalladiumdi[1,1′-bis(diphenylphospino)ferrocene]dichloride(PdCl₂(dppf)), and the resulting solution was stirred overnight at 90°C. The resulting reaction mixture was filtered through a celite pad andconcentrated under reduced pressure to give a residue. The residue thusobtained was dissolved in ethylacetate, washed with distilled water,dried over anhydrous magnesium sulfate, and concentrated under reducedpressure to give a yellow liquid residue. The residue was purified withsilica gel column chromatography (developing solvent: n-hexane/ethylacetate=1/1) to give 53 mg of the title compound (yield: 64.8%). MS(ESI) m/z=421.1 (M+H)+

Step 2:2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one

53 mg of tert-butyl N-[3,3-difluoro-2-[[4-[3-(4-methylsulfonylphenyl)phenyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamateprepared in Step 1 was dissolved in 1.0 mL of dichloromethane, followedby the addition of 0.1 mL of trifluoroacetic acid, the resultingsolution was stirred at room temperature for 2 hours. The reactionmixture thus obtained was concentrated, followed by the addition ofdichloromethane. The solution was concentrated under reduced pressureand then dried in vacuo to obtain a yellow liquid residue. The residuewas purified with silica gel column chromatography (developing solvent:dichloromethane/methanol=10/1) to give 40 mg of the title compound as awhite solid (yield: 93.1%). ¹H-NMR (MeOD, 400 MHz) δ 8.36 (s, 1H),8.07-7.95 (m, 4H), 7.76-7.66 (m, 4H), 4.66 (s, 2H), 3.50 (s, 2H), 2.22(s, 3H)

Example 18.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-oneditrifluoroacetate

35 mg of the title compound (yield: 35.6%) was prepared in the samefashion as Example 17, except that in Step 1, 61 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.33 (s, 1H), 7.88 (s, 1H), 7.66-7.55 (m, 5H), 7.14 (d, 2H),4.67 (s, 2H), 3.71 (s, 2H), 3.49-3.46 (m, 4H), 3.40-3.37 (m, 4H)

Example 19.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-onetrifluoroacetate

36 mg of the title compound (yield: 44.8%) was prepared in the samefashion as Example 17, except that 43 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid in Step 1. ¹H-NMR(MeOD, 400 MHz) δ 9.05 (s, 1H), 8.41 (s, 1H), 8.36 (d, 1H), 8.06 (s,1H), 7.94 (d, 1H), 7.83-7.72 (m, 3H), 4.68 (s, 2H), 3.74 (s, 2H)

Example 20.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]phenyl]-1,2,4-triazol-3-onetrifluoroacetate

38 mg of the title compound (yield: 49.7%) was prepared in the samefashion as Example 17, except that 39 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid in Step 1. ¹H-NMR (MeOD, 400 MHz)δ 8.37 (s, 1H), 8.28 (d, 2H), 7.93 (s, 1H), 7.70-7.65 (m, 3H), 7.26 (d,1H), 4.68 (s, 2H), 3.76 (s, 2H), 3.32 (s, 6H)

Example 21.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1,2,4-triazol-3-onetrifluoroacetate

62 mg of the title compound (yield: 81.2%) was prepared in the samefashion as Example 17, except that 39 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid in Step 1. ¹H-NMR(MeOD, 400 MHz) δ 8.33 (s, 1H), 7.83 (s, 1H), 7.57-7.55 (m, 3H), 7.18(s, 1H), 6.91 (s, 2H), 6.01 (s, 2H), 4.66 (s, 2H), 3.67 (s, 2H)

Example 22.6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

33 mg of the title compound (yield: 40.0%) was prepared in the samefashion as Example 17, except that 45 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid in Step 1.¹H-NMR (MeOD, 400 MHz) δ 8.34 (s, 1H), 7.87 (s, 1H), 7.65 (t, 1H),7.59-7.56 (m, 2H), 7.39 (s, 2H), 4.66 (s, 2H), 3.64 (s, 2H), 3.02 (t,2H), 2.60 (t, 2H)

Example 23.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)phenyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 48.4%) was prepared in the samefashion as Example 17, except that X mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid in Step 1. ¹H-NMR (MeOD, 400 MHz) δ 8.32 (s, 1H), 8.11 (s, 1H),7.91 (s, 1H), 7.83 (s, 1H), 7.62 (d, 1H), 7.54-7.47 (m, 2H), 4.67 (d,2H), 4.23 (q, 2H), 3.75 (s, 2H), 1.50 (t, 3H)

Example 24.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 52.8%) was prepared in the samefashion as Example 17, except that 50 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used in Step 1, instead oftert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.38 (s, 1H),8.08 (d, 1H), 7.86 (d, 1H), 7.79-7.67 (m, 3H), 4.63 (s, 2H), 3.18 (s,3H)

Example 25.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-oneditrifluoroacetate

21 mg of the title compound (yield: 43.7%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 54 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.36 (s, 1H), 7.67-7.53 (m, 5H), 7.14 (d, 2H), 4.66 (s, 2H),3.71 (s, 2H), 3.51-3.39 (m, 8H)

Example 26.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-onetrifluoroacetate

33 mg of the title compound (yield: 71.2%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 38 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.94 (s, 1H), 8.40 (s, 1H), 8.28 (d, 1H), 7.95 (d, 1H), 7.85-7.72 (m,3H), 4.64 (s, 2H), 3.39 (s, 2H)

Example 27.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-3-fluoro-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

24 mg of the title compound (yield: 55.0%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 35 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.40 (s,1H), 8.19 (s, 1H), 8.12 (d, 1H), 7.78-7.64 (m, 3H), 7.21 (d, 1H), 4.67(s, 2H), 3.75 (s, 2H), 3.32 (s, 6H)

Example 28.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-3-fluoro-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

31 mg of the title compound (yield: 71.0%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 35 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.36 (s, 1H), 7.67-7.54 (m, 3H), 7.06 (s, 2H), 6.94 (d, 1H), 6.02(s, 2H), 4.65 (s, 2H), 3.66 (s, 2H)

Example 29.6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-fluoro-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

27 mg of the title compound (yield: 56.4%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 40 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.36 (s, 1H), 7.67-7.54 (m, 3H), 7.26 (s, 2H), 4.67 (s, 2H),3.75 (s, 2H), 3.00 (t, 2H), 2.60 (t, 2H), 2.32 (s, 3H)

Example 30.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-3-fluoro-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

28 mg of the title compound (yield: 81.4%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-3-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 27 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 31 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.33 (s, 1H), 8.13 (s, 1H), 7.95 (s, 1H),7.83 (t, 1H), 7.64 (d, 1H), 7.51 (d, 1H), 4.64 (s, 2H), 4.26 (q, 2H),3.62 (s, 2H), 1.51 (t, 3H)

Example 31.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 61.2%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.19 (s, 1H),8.08 (d, 2H), 7.97 (d, 2H), 7.81-7.72 (m, 3H), 4.68 (s, 2H), 3.76 (s,2H), 3.18 (s, 3H)

Example 32.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-oneditrifluoroacetate

22 mg of the title compound (yield: 45.8%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 54 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.14 (s, 1H), 7.64-7.60 (m, 5H), 7.14 (d, 2H), 4.67 (s, 2H),3.73 (s, 2H), 3.50-3.40 (m, 8H)

Example 33.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 53.9%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25, and 38 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.19 (s, 1H), 8.08 (d, 2H), 7.97 (d, 2H), 7.81-7.72 (m, 3H), 4.68 (s,2H), 3.76 (s, 2H), 3.18 (s, 3H)

Example 34.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-fluoro-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 80.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 35 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.30-8.16 (m, 3H), 7.74-7.62 (m, 3H), 7.20 (d, 1H), 4.67 (s, 2H), 3.73(s, 2H), 1.87 (s, 6H)

Example 35.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-fluoro-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

30 mg of the title compound (yield: 68.7%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 35 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.13 (s, 1H), 7.64-7.53 (m, 3H), 7.18 (s, 2H), 6.94 (s, 1H), 6.02(d, 2H), 4.67 (s, 2H), 3.73 (s, 2H)

Example 36.6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-fluoro-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

33 mg of the title compound (yield: 68.9%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 40 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 9.06 (s, 1H), 8.36 (s, 1H), 8.17 (s, 1H), 7.95-7.76 (m, 4H),4.65 (s, 2H), 3.49 (s, 2H)

Example 37.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-fluoro-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 61.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-fluoro-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 28 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 31 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.16 (s, 1H), 8.11 (s, 1H), 7.93 (s, 1H),7.61-7.56 (m, 3H), 4.65 (s, 2H), 4.23 (q, 2H), 3.63 (s, 2H), 1.50 (t,3H)

Example 38.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 44.0%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 9.04 (s, 1H),8.44 (s, 1H), 8.30 (d, 2H), 8.24 (d, 1H), 8.13 (d, 1H), 8.06 (d, 2H),4.69 (s, 2H), 3.77 (s, 2H), 3.18 (s, 3H)

Example 39.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-3-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

32 mg of the title compound (yield: 55.9%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 52 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.37 (s, 1H), 8.12 (d, 1H), 8.00-7.95 (m, 3H), 7.14 (d, 2H)4.67 (s, 2H), 3.73 (s, 2H), 3.53 (t, 4H), 3.39 (t, 4H)

Example 40.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

17 mg of the title compound (yield: 29.8%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 37 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 9.41 (s, 1H), 9.10 (s, 1H), 8.71 (d, 1H), 8.46 (s, 1H), 8.31 (d, 1H),8.23 (d, 1H), 7.96 (d, 1H), 4.69 (s, 2H), 3.77 (s, 2H)

Example 41.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

19 mg of the title compound (yield: 37.3%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 33 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 9.00 (s,1H), 8.68 (d, 1H), 8.65 (s, 1H), 8.42 (s, 1H), 8.23 (d, 1H), 8.07 (d,1H), 7.35 (d, 1H), 4.68 (s, 2H), 3.36 (s, 3H)

Example 42.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

26 mg of the title compound (yield: 50.0%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 33 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.37 (s, 1H), 8.11 (d, 1H), 7.93 (d, 1H), 7.57 (d, 1H), 7.55 (s,1H), 6.94 (d, 1H), 6.04 (s, 2H), 4.67 (s, 2H), 3.76 (s, 2H)

Example 43.6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

17 mg of the title compound (yield: 29.8%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 39 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.89 (s, 1H), 8.38 (s, 1H), 8.11 (d, 1H), 7.94 (d, 1H), 7.71(s, 2H), 4.68 (s, 2H), 3.77 (s, 2H), 3.01 (t, 2H), 2.60 (t, 4H), 2.33(s, 3H)

Example 44.6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

22 mg of the title compound (yield: 39.6%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 39 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 8.90 (s, 1H), 8.38 (s, 1H), 8.11 (d, 1H), 7.96-7.86(m, 3H), 7.17 (d, 1H), 4.68 (s, 2H), 3.34 (s, 3H), 2.96 (t, 2H), 2.64(t, 2H)

Example 45.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

22 mg of the title compound (yield: 45.4%) was prepared in the samefashion as Example 17, except that in Step 1, 60 mg of tert-butylN-[2-[[4-(6-bromo-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 30 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 30 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.35 (s, 1H), 8.26 (s, 1H), 8.07 (s, 2H),7.80 (d, 1H) 4.67 (s, 2H), 4.27 (q, 2H), 3.75 (s, 2H), 1.52 (t, 3H)

Example 46.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 74.2%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.85 (s, 1H),8.37 (d, 2H), 8.28 (d, 1H), 8.07 (t, 3H), 7.99 (d, 1H), 4.68 (s, 2H),3.77 (s, 2H), 3.18 (s, 3H)

Example 47.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

33 mg of the title compound (yield: 68.9%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 52 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.79 (s, 1H), 8.07 (d, 3H), 7.95 (t, 1H), 7.80 (d, 1H), 7.13(d, 2H), 4.67 (s, 2H), 3.72 (s, 2H), 3.53 (s, 4H), 3.39 (s, 4H)

Example 48.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

28 mg of the title compound (yield: 60.6%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 26 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 9.44 (s, 1H), 8.88 (s, 1H), 8.75 (d, 1H), 8.33 (d, 1H), 8.13 (t, 1H),8.05 (d, 1H), 7.95 (d, 1H), 4.69 (s, 2H), 3.77 (s, 2H)

Example 49.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 57.6%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 33 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.83 (s,1H), 8.70 (s, 1H), 8.63 (d, 1H), 8.21 (d, 1H), 8.05 (t, 1H), 7.86 (d,1H), 7.24 (d, 1H), 4.68 (s, 2H), 3.76 (s, 2H), 3.34 (s, 6H)

Example 50.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

36 mg of the title compound (yield: 83.0%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.76 (s, 1H), 8.07 (d, 1H), 7.93 (t, 1H), 7.73 (d, 1H), 7.61 (d,2H), 6.90 (d, 1H), 6.02 (s, 2H), 4.66 (s, 2H), 3.75 (s, 2H)

Example 51.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

29 mg of the title compound (yield: 60.7%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 39 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.81 (s, 1H), 8.10 (d, 1H), 7.96 (t, 1H), 7.80 (s, 3H), 4.68(s, 2H), 3.76 (s, 2H), 3.03 (t, 2H), 2.61 (t, 2H), 2.34 (s, 3H)

Example 52.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

36 mg of the title compound (yield: 75.4%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 39 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 8.82 (s, 1H), 8.12 (d, 1H), 8.01-7.96 (m, 3H), 7.83(d, 1H), 7.18 (d, 1H), 4.68 (s, 2H), 3.76 (s, 2H), 3.36 (s, 3H), 3.00(t, 2H), 2.66 (t, 2H)

Example 53.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

24 mg of the title compound (yield: 59.3%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 30 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.81 (s, 1H), 8.32 (s, 1H), 8.09 (s, 1H),8.02 (d, 1H), 7.89 (t, 1H), 7.58 (d, 1H), 4.66 (s, 3H), 4.25 (q, 2H),3.75 (s, 2H), 1.51 (t, 3H)

Example 54.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

34 mg of the title compound (yield: 72.0%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.68 (s, 1H),8.58 (d, 2H), 8.12 (d, 2H), 8.04 (d, 2H), 7.72 (s, 1H), 4.66 (s, 2H),3.66 (s, 2H), 3.20 (s, 3H)

Example 55.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

25 mg of the title compound (yield: 52.2%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 52 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.65 (s, 1H), 8.47 (d, 2H), 7.76 (d, 2H), 7.62 (s, 1H), 7.16(d, 2H), 4.67 (s, 2H), 3.67 (s, 2H), 3.51 (d, 4H), 3.36 (d, 4H)

Example 56.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 62.8%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 31 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 9.11 (s, 1H), 8.68 (s, 1H), 8.59 (s, 2H), 8.42 (d, 1H), 7.99 (d, 1H),7.75 (d, 1H), 4.67 (s, 2H), 3.63 (s, 2H)

Example 57.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

30 mg of the title compound (yield: 69.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 28 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.68 (s,1H), 8.52 (s, 1H), 8.46 (d, 2H), 8.25 (d, 1H), 7.65 (s, 1H), 7.19 (d,1H), 4.69 (s, 2H), 3.76 (s, 2H), 3.31 (s, 3H)

Example 58.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

26 mg of the title compound (yield: 59.9%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 28 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.63 (s, 1H), 8.42 (d, 2H), 7.56 (s, 1H), 7.32-7.28 (m, 2H), 6.97(d, 1H), 6.06 (s, 2H), 4.66 (s, 2H), 3.54 (s, 2H)

Example 59.6-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-4-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

25 mg of the title compound (yield: 52.3%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 33 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.61 (s, 1H), 8.44 (d, 2H), 7.60 (d, 1H), 7.50 (d, 2H), 4.64(s, 2H), 3.36 (s, 2H), 3.04 (d, 2H), 2.62 (d, 2H)

Example 60.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

24 mg of the title compound (yield: 59.3%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 32 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 26 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.62 (s, 1H), 8.37-8.29 (m, 3H), 8.02 (s,1H), 7.53 (s, 1H), 4.68 (s, 2H), 4.26 (q, 2H), 3.76 (s, 2H), 1.52 (t,3H)

Example 61.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-methylsulfonylphenyl)-4-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

45 mg of the title compound (yield: 47.7%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.78 (s, 1H),8.63 (s, 1H), 8.41 (s, 1H), 8.29 (s, 1H), 8.07 (d, 2H), 7.91 (s, 1H),4.68 (s, 2H), 3.76 (s, 2H), 3.18 (s, 3H)

Example 62.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-piperazin-1-ylphenyl)-4-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

50 mg of the title compound (yield: 52.2%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 87 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.67 (d, 1H), 8.61 (s, 1H), 8.27 (s, 2H), 7.99 (d, 2H), 7.75(d, 1H), 7.16 (d, 2H), 4.68 (s, 2H), 3.75 (s, 2H), 3.55 (t, 4H), 3.40(t, 4H)

Example 63.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[6-(dimethylamino)-3-pyridyl]-4-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

40 mg of the title compound (yield: 46.1%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 56 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.75 (d,1H), 8.65 (d, 3H), 8.34 (s, 1H), 7.90 (d, 1H), 7.36 (d, 1H), 4.68 (s,2H), 3.76 (s, 2H), 3.37 (s, 6H)

Example 64.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1,3-benzodioxol-5-yl)-4-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

38 mg of the title compound (yield: 43.8%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 67 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.63 (d, 1H), 8.59 (s, 1H), 8.19 (s, 1H), 7.78 (d, 1H), 7.52 (d,1H), 7.49 (s, 1H), 6.93 (d, 1H), 4.67 (s, 2H), 3.75 (s, 2H)

Example 65.6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

42 mg of the title compound (yield: 44.0%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 64 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.66 (d, 1H), 8.64 (s, 1H), 8.27 (s, 1H), 7.82 (d, 1H), 7.71(s, 2H), 3.03 (t, 2H), 2.61 (t, 2H), 2.29 (s, 3H)

Example 66.6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

46 mg of the title compound (yield: 48.2%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 64 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 8.76 (d, 1H), 8.74 (s, 1H), 8.52 (s, 1H), 8.13 (s,1H), 7.95 (d, 1H), 7.90 (s, 1H), 7.32 (d, 1H), 4.69 (s, 2H), 3.76 (s,2H), 3.41 (s, 3H), 3.05 (t, 2H), 2.70 (t, 2H)

Example 67.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1-ethylpyrazol-4-yl)-4-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

42 mg of the title compound (yield: 51.9%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(2-bromo-4-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 33 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 50 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.60 (s, 1H), 8.58 (d, 1H), 8.28 (s, 1H),8.10 (d, 2H), 7.76 (d, 1H), 4.67 (s, 2H), 4.26 (q, 2H), 3.75 (s, 2H),1.52 (t, 3H)

Example 68.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one trifluoroacetate

38 mg of the title compound (yield: 80.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.74 (s, 1H),8.25 (s, 1H), 8.21 (s, 1H), 8.09 (d, 2H), 7.99 (d, 2H), 4.69 (s, 2H),3.77 (s, 2H), 3.19 (s, 3H), 2.45 (s, 3H)

Example 69.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

39 mg of the title compound (yield: 81.0%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 51 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.63 (s, 1H), 8.16 (s, 1H), 8.11 (s, 1H), 7.68 (d, 2H), 7.17(d, 2H), 4.68 (s, 2H), 3.73 (s, 2H), 3.51 (s, 4H), 3.40 (s, 4H), 2.40(s, 3H)

Example 70.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 75.3%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 9.09 (s, 1H), 8.80 (s, 1H), 8.41 (d, 1H), 8.32 (s, 1H), 8.22 (s, 1H),7.98 (d, 1H), 4.69 (s, 2H), 3.77 (s, 2H), 2.47 (s, 3H)

Example 71.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

30 mg of the title compound (yield: 68.6%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 32 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.68 (s,1H), 8.35 (s, 1H), 8.24 (d, 1H), 8.18 (s, 2H), 7.21 (d, 1H), 4.68 (s,2H), 3.76 (s, 2H), 3.31 (s, 6H), 2.43 (s, 3H)

Example 72.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 73.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of 3,4-(methylenedioxy)phenylboronic acid was used instead of 4-(methanesulfonyl)phenylboronic acid.¹H-NMR (MeOD, 400 MHz) δ 8.59 (s, 1H), 8.16 (s, 1H), 8.07 (s, 1H), 7.21(s, 1H), 7.20 (d, 1H), 6.96 (d, 1H), 6.03 (s, 2H), 4.68 (s, 2H), 3.76(s, 2H), 2.40 (s, 3H)

Example 73.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

40 mg of the title compound (yield: 83.3%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 37 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.54 (s, 1H), 8.16 (s, 1H), 8.06 (s, 1H), 7.36 (d, 2H), 4.70(s, 2H), 3.78 (s, 2H), 3.01 (t, 2H), 2.59 (t, 2H), 2.40 (s, 3H), 2.29(s, 3H)

Example 74.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

42 mg of the title compound (yield: 87.5%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 37 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 8.65 (s, 1H), 8.16 (d, 2H), 7.64 (d, 1H), 7.60 (s,1H), 7.25 (d, 1H), 4.69 (s, 2H), 3.77 (s, 2H), 3.39 (s, 3H), 3.01 (t,2H), 2.67 (t, 2H), 2.42 (s, 3H)

Example 75.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 78.2%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 29 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.63 (s, 1H), 8.23 (s, 1H), 8.15 (s, 1H),8.09 (s, 1H), 7.99 (s, 1H), 4.68 (s, 2H), 4.25 (q, 2H), 3.75 (s, 2H),2.36 (s, 3H), 1.51 (t, 3H)

Example 76.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazol-3-one trifluoroacetate

25 mg of the title compound (yield: 52.3%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 36 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.87 (s, 1H),8.43 (s, 1H), 8.15-8.08 (m, 3H), 7.81 (d, 2H), 4.69 (s, 2H), 3.77 (s,2H), 3.20 (s, 3H), 2.44 (s, 3H)

Example 77.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

17 mg of the title compound (yield: 35.8%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 36 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 30 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.93 (s, 2H), 8.45 (s, 1H), 8.27 (s, 1H), 8.19 (s, 1H), 7.97 (s, 1H),4.68 (s, 2H), 3.77 (s, 2H), 2.49 (s, 3H)

Example 78.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-5-methyl-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

19 mg of the title compound (yield: 44.0%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 36 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 27 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.83 (s,1H), 8.40 (s, 1H), 8.23 (s, 1H), 8.10 (s, 1H), 8.02 (s, 1H), 7.06 (s,1H), 4.68 (s, 2H), 3.76 (s, 2H), 3.26 (s, 6H), 2.50 (s, 3H)

Example 79.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-5-methyl-3-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

26 mg of the title compound (yield: 59.6%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 36 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 27 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.76 (s, 1H), 8.39 (s, 1H), 8.07 (s, 1H), 7.01-6.96 (m, 3H), 6.04(s, 2H), 4.67 (s, 2H), 3.76 (s, 2H), 2.43 (s, 3H)

Example 80.6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

17 mg of the title compound (yield: 35.8%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 36 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 32 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.77 (s, 1H), 8.40 (s, 1H), 8.07 (s, 1H), 7.23 (s, 2H), 4.68(s, 2H), 3.77 (s, 2H), 3.02 (t, 2H), 2.62 (t, 2H), 2.44 (s, 3H), 2.34(s, 3H)

Example 81.6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

22 mg of the title compound (yield: 46.8%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-5-methyl-3-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 36 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 32 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 8.80 (s, 1H), 8.41 (s, 1H), 8.09 (s, 1H), 7.46 (d,1H), 7.42 (s, 1H), 7.25 (d, 1H), 4.68 (s, 2H), 3.77 (s, 2H), 3.42 (s,3H), 3.01 (t, 2H), 2.69 (t, 2H), 2.45 (s, 3H)

Example 82.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one trifluoroacetate

23 mg of the title compound (yield: 48.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.77 (s, 1H),8.31 (s, 1H), 8.28 (s, 1H), 8.11 (d, 2H), 8.02 (d, 2H), 4.69 (s, 2H),3.77 (s, 2H), 3.19 (s, 3H)

Example 83.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

18 mg of the title compound (yield: 38.9%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 42 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.67 (s, 1H), 8.24 (s, 1H), 8.12 (d, 1H), 7.72 (d, 2H), 7.18(d, 2H), 4.68 (s, 2H), 3.76 (s, 2H), 3.54 (t, 4H), 3.41 (t, 4H)

Example 84.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 44.4%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 29 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 9.13 (s, 1H), 8.83 (s, 1H), 8.44 (d, 2H), 8.29 (s, 1H), 8.00 (s, 1H),4.69 (s, 2H), 3.77 (s, 2H)

Example 85.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 74.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 27 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.60 (s, 1H), 8.22 (s, 1H), 8.07 (d, 1H), 7.24 (s, 1H), 7.22 (s,1H), 6.96 (d, 1H), 6.04 (s, 2H), 4.68 (s, 2H), 3.74 (s, 2H)

Example 86.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

17 mg of the title compound (yield: 35.2%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 31 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.58 (s, 1H), 8.23 (s, 1H), 8.07 (d, 1H), 7.41 (s, 1H), 4.69(s, 2H), 3.78 (s, 2H), 3.01 (t, 2H), 2.59 (t, 2H), 2.31 (s, 3H)

Example 87.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

18 mg of the title compound (yield: 38.9%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 31 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 8.68 (s, 1H), 8.25 (s, 1H), 8.17 (d, 1H), 7.68 (d,1H), 7.64 (s, 1H), 7.27 (d, 1H), 4.68 (s, 2H), 3.77 (s, 2H), 3.39 (s,3H), 3.02 (t, 2H), 2.66 (t, 2H)

Example 88.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

18 mg of the title compound (yield: 45.4%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-fluoro-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 37 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 37 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.65 (s, 1H), 8.28 (s, 1H), 8.21 (s, 1H),8.10 (d, 1H), 8.03 (s, 1H), 4.67 (s, 2H), 4.26 (q, 2H), 3.75 (s, 2H),1.50 (t, 3H)

Example 89.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-methylsulfonylphenyl)-pyrazin-2-yl]-1,2,4-triazol-3-onetrifluoroacetate

38 mg of the title compound (yield: 57.3%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 9.53 (s, 1H),9.04 (s, 1H), 8.63 (s, 1H), 8.30 (d, 2H), 8.03 (d, 2H), 4.69 (s, 2H),3.78 (s, 2H), 3.17 (s, 3H)

Example 90.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-piperazin-1-ylphenyl)pyrazin-2-yl]-1,2,4-triazol-3-oneditrifluoroacetate

30 mg of the title compound (yield: 44.6%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 61 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 9.45 (s, 1H), 8.98 (s, 1H), 8.63 (s, 1H), 8.07 (d, 2H), 7.18(d, 2H), 4.68 (s, 2H), 3.76 (s, 2H), 3.56 (t, 4H), 3.41 (t, 4H)

Example 91.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(trifluoromethyl)-3-pyridyl]pyrazin-2-yl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 49.3%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 43 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 9.64 (s, 1H), 9.43 (s, 1H), 9.20 (s, 1H), 8.75 (d, 1H), 8.68 (s, 2H),7.98 (d, 1H), 4.69 (s, 2H), 3.78 (s, 2H)

Example 92.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]pyrazin-2-yl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 47.6%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 39 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 9.48 (s,1H), 8.97 (s, 1H), 8.76 (s, 1H), 8.63 (s, 1H), 8.44 (d, 1H), 7.05 (d,1H), 4.68 (s, 2H), 3.76 (s, 2H), 3.32 (s, 6H)

Example 93.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)pyrazin-2-yl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 57.4%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 39 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 9.44 (s, 1H), 8.91 (s, 1H), 8.61 (s, 1H), 7.64 (d, 1H), 7.60 (s,1H), 6.96 (d, 1H), 6.05 (s, 2H), 4.67 (s, 2H), 3.69 (s, 2H)

Example 94.6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]pyrazin-2-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

41 mg of the title compound (yield: 61.1%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 45 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 9.47 (s, 1H), 8.98 (s, 1H), 8.64 (s, 1H), 8.03 (d,1H), 7.99 (s, 1H), 7.25 (d, 1H), 4.68 (s, 2H), 3.77 (s, 2H), 3.39 (s,3H), 3.03 (t. 2H), 2.68 (t, 2H)

Example 95.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)pyrazin-2-yl]-1,2,4-triazol-3-onetrifluoroacetate

39 mg of the title compound (yield: 68.6%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromopyrazin-2-yl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 39 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 35 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 9.37 (s, 1H), 8.79 (s, 1H), 8.60 (s, 1H),8.34 (s, 1H), 8.12 (s, 1H), 4.67 (s, 1H), 4.27 (q, 2H), 3.92 (s, 2H),1.52 (t, 3H)

Example 96.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-benzyloxyphenyl)methyl]-1,2,4-triazol-3-onetrifluoroacetate

17 mg of the title compound (yield: 8.5%) as a colorless liquid wasprepared in the same fashion as Example 1, except that 126 mg oftert-butylN-[2-[[4-[(4-benzyloxyphenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 40 was used. ¹H-NMR (MeOD, 400 MHz) δ 7.88(s, 1H), 7.41-7.36 (m, 4H), 7.29 (d, 3H), 6.99 (d, 2H), 5.08 (s, 2H),4.79 (s, 2H), 4.57 (s, 2H), 3.66 (s, 2H)

Example 97.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-2-thienyl)methyl]-1,2,4-triazol-3-onetrifluoroacetate

92 mg of the title compound (yield: 1.0%) was prepared in the samefashion as Example 1, except that 116 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used. ¹H-NMR (MeOD, 400 MHz) δ 7.96(s, 1H), 6.98 (d, 2H), 5.00 (s, 2H), 4.58 (s, 2H), 3.67 (s, 2H)

Example 98.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-bromo-2-thienyl)methyl]-1,2,4-triazol-3-onetrifluoroacetate

34 mg of the title compound (yield: 76.0%) was prepared in the samefashion as Example 1, except that 57 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used. ¹H-NMR (MeOD, 400 MHz) δ 7.97(s, 1H), 7.40 (s, 1H), 7.12 (s, 1H), 5.04 (s, 2H), 4.57 (s, 2H), 3.66(s, 2H).

Example 99.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-3-methyl-2-thienyl)methyl]-1,2,4-triazol-3-onetrifluoroacetate

16 mg of the title compound (yield: 3.7%) was prepared in the samefashion as Example 1, except that 546 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 43 was used. ¹H-NMR (MeOD, 400 MHz) δ 7.90(s, 1H), 6.90 (s, 1H), 4.94 (s, 2H), 4.57 (s, 2H), 3.67 (s, 2H), 2.27(s, 3H)

Example 100.4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-onetrifluoroacetate Step 1: tert-butylN-[2-[[4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamate

80 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 28 m of 4-acetylphenylboronicacid28 were dissolved in 1.6 mL of 1,4-dioxane, followed by the addition of0.9 mL of 1 M potassium carbonate and 7 mg ofpalladiumdi[1,1′-bis(diphenylphospino)ferrocene]dichloride(PdCl₂(dppf)), and the resulting solution was stirred overnight at 90°C. The resulting reaction mixture was filtered through a celite pad andconcentrated under reduced pressure to give a residue. The residue thusobtained was dissolved in ethylacetate, washed with distilled water,dried over anhydrous magnesium sulfate, and concentrated under reducedpressure to give a yellow liquid residue. The residue was purified withsilica gel column chromatography (developing solvent: n-hexane/ethylacetate=1/1) to give 47 mg of the title compound (yield: 54.2%). MS(ESI) m/z=405.2 (M+H)+

Step 2:4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one

47 mg of tert-butylN-[2-[[4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Step 1 was dissolved in 1.0 mL of dichloromethane, followedby the addition of 0.1 mL of trifluoroacetic acid, and the resultingsolution was stirred at room temperature for 2 hours. The reactionmixture thus obtained was concentrated, followed by the addition ofdichloromethane. The solution was concentrated under reduced pressureand then dried in vacuo to obtain a yellow liquid residue. The residuewas purified with silica gel column chromatography (developing solvent:dichloromethane/methanol=10/1) to give 4 mg of the title compound as awhite solid (yield: 12.0%). ¹H-NMR (MeOD, 400 MHz) δ 8.00 (s, 1H), 7.99(d, 2H), 7.72 (d, 2H), 7.43 (s, 1H), 7.18 (s, 1H), 5.09 (s, 2H), 4.60(s, 2H), 3.69 (s, 2H), 2.60 (s, 3H)

Example 101.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

42 mg of the title compound (yield: 82.2%) was prepared in the samefashion as Example 100, except that in Step 1, 26 mg of4-(methanesulfonyl)phenylboronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.01 (s, 1H), 7.94(d, 2H), 7.84 (d, 2H), 7.48 (s, 1H), 7.19 (s, 1H), 5.10 (s, 2H), 4.59(s, 2H), 3.68 (s, 2H), 3.14 (s, 3H)

Example 102. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one trifluoroacetate

8 mg of the title compound (yield: 11.0%) was prepared in the samefashion as Example 100, except that in Step 1, 34 mg of3-(methanesulfonyl)phenylboronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.11 (s, 1H), 8.00(s, 1H), 7.92-7.86 (m, 2H), 7.64 (t, 1H), 7.42 (s, 1H), 7.17 (s, 1H),5.09 (s, 2H), 4.60 (s, 2H), 3.69 (s, 2H), 3.17 (s, 3H)

Example 103.3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N,N-dimethyl-benzenesulfonamidetrifluoroacetate

16 mg of the title compound (yield: 17.6%) was prepared in the samefashion as Example 100, except that in Step 1, 54 mg of3-(N,N-dimethylaminosulfonyl)phenylboronic acid pinacol ester was usedinstead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.00 (s,1H), 7.92 (s, 2H), 7.72-7.63 (m, 2H), 7.42 (s, 1H), 7.19 (s, 1H), 5.10(s, 2H), 4.60 (s, 2H), 3.68 (s, 2H), 2.72 (s, 6H)

Example 104.4-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N-methyl-benzamidetrifluoroacetate

22 mg of the title compound (yield: 29.4%) was prepared in the samefashion as Example 100, except that in Step 1, 36 mg of(4-(methylcarbamoyl)phenyl)boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.00 (s, 1H), 7.83(d, 2H), 7.69 (d, 2H), 7.39 (s, 1H), 7.16 (s, 1H), 5.08 (s, 2H), 4.59(s, 2H), 3.68 (s, 2H), 2.93 (s, 3H)

Example 105.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3,4,5-trimethoxyphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

22 mg of the title compound (yield: 45.4%) was prepared in the samefashion as Example 100, except that in Step 1, 23 mg of3,4,5-trimethoxyphenylboronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H), 7.24(s, 1H), 7.12 (s, 1H), 6.85 (s, 2H), 5.05 (s, 2H), 4.59 (s, 2H), 3.88(s, 6H), 3.78 (s, 3H), 3.67 (s, 2H)

Example 106.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

40 mg of the title compound (yield: 81.8%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.97 (s, 1H), 7.52 (d, 2H), 7.15 (s, 1H), 7.09 (s, 1H), 7.03 (d, 2H),5.04 (s, 2H), 4.59 (s, 2H), 3.66 (s, 2H), 3.45 (s, 4H), 3.38 (s, 4H)

Example 107.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

11 mg of the title compound (yield: 18.2%) was prepared in the samefashion as Example 100, except that in Step 1, 51 mg of tert-butyl4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylatewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.98 (s, 1H), 7.33-7.29 (m, 2H), 7.22 (s, 1H), 7.18-7.13 (m, 2H), 6.99(d, 1H), 5.06 (s, 2H), 4.59 (s, 2H), 3.64 (s, 2H), 3.45 (t, 4H), 3.38(t, 4H)

Example 108.4-[[5-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-onetrifluoroacetate

695 mg of the title compound (yield: 66.0%) was prepared in the samefashion as Example 100, except that in Step 1, 923 mg of4-(4-acetyl-1-piperazinyl)phenylboronic acid pinacol ester was usedinstead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.97 (s,1H), 7.49 (d, 2H), 7.14 (d, 1H), 7.09 (d, 1H), 7.00 (d, 2H), 5.03 (s,2H), 4.59 (s, 2H), 3.74 (t, 2H), 3.71 (t, 2H), 3.66 (s, 2H), 3.26 (t,2H), 3.21 (t, 2H), 2.16 (s, 3H)

Example 109.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-morpholine-4-carbonyl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

23 mg of the title compound (yield: 29.4%) was prepared in the samefashion as Example 100, except that in Step 1, 54 mg of4-(morpholine-4-carbonyl)phenylboronic acid pinacol ester was usedinstead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.00 (s,1H), 7.71 (d, 2H), 7.47 (d, 2H), 7.38 (s, 1H), 7.16 (s, 1H), 5.08 (s,2H), 4.59 (s, 2H), 3.75-3.50 (m, 8H), 3.68 (s, 2H)

Example 110.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-pyrazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

6 mg of the title compound (yield: 5.9%) was prepared in the samefashion as Example 100, except that in Step 1, 32 mg of[3-(1H-pyrazol-3-yl)phenyl]boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.04 (s, 1H), 8.00(s, 1H), 7.70 (s, 2H), 7.56 (d, 1H), 7.46 (t, 1H), 7.37 (s, 1H), 7.17(s, 1H), 6.73 (s, 1H), 5.09 (s, 2H), 4.60 (s, 2H), 3.65 (s, 2H)

Example 111.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

7 mg of the title compound (yield: 9.1%) was prepared in the samefashion as Example 100, except that in Step 1, 25 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.97 (s,1H), 8.24 (d, 1H), 8.02 (s, 1H), 7.84 (d, 1H), 7.57 (s, 1H), 7.24 (s,1H), 5.12 (s, 2H), 4.59 (s, 2H), 3.67 (s, 2H)

Example 112.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

45 mg of the title compound (yield: 1.0%) was prepared in the samefashion as Example 100, except that in Step 1, 32 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.11 (d, 2H), 7.99(s, 1H), 7.28 (s, 1H), 7.17 (s, 2H), 5.08 (s, 2H), 4.59 (s, 2H), 3.68(s, 2H), 3.28 (s, 6H)

Example 113.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-methoxy-3-pyridyl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 41.2%) was prepared in the samefashion as Example 100, except that in Step 1, 40 mg of2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine wasused instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.34(s, 1H), 7.99 (s, 1H), 7.88 (d, 1H), 7.21 (s, 1H), 7.14 (s, 1H), 6.83(d, 1H), 5.06 (s, 2H), 4.59 (s, 2H), 3.93 (s, 3H), 3.68 (s, 2H)

Example 114.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-piperazin-1-yl-3-pyridyl)-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

35 mg of the title compound (yield: 72.7%) was prepared in the samefashion as Example 100, except that in Step 1, 54 mg of tert-butyl4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]piperazine-1-carboxylatewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.41 (s, 1H), 7.98 (s, 1H), 7.83 (d, 1H), 7.15 (d, 2H), 6.96 (d, 1H),5.06 (s, 2H), 4.59 (s, 2H), 3.85 (s, 4H), 3.68 (s, 2H), 3.32 (s, 4H)

Example 115.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-5-fluoro-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

26 mg of the title compound (yield: 35.3%) was prepared in the samefashion as Example 100, except that in Step 1, 46 mg of3-fluoro-N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-aminewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.13 (s, 1H), 7.98 (s, 1H), 7.54 (d, 1H), 7.17 (s, 1H), 7.11 (s, 1H),5.05 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H), 3.11 (s, 6H)

Example 116.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-aminopyrimidin-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 41.2%) was prepared in the samefashion as Example 100, except that in Step 1, 55 mg of2-(tert-butoxycarbonylamino)pyrimidine-5-boronic acid pinacol ester wasused instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.47(s, 2H), 7.98 (s, 1H), 7.15 (d, 2H), 5.06 (s, 2H), 4.59 (s, 2H), 3.66(s, 2H)

Example 117.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-ethoxypyrimidin-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 29.4%) was prepared in the samefashion as Example 100, except that in Step 1, 29 mg of2-ethoxypyrimidin-5-boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.76 (s, 2H), 8.00(s, 1H), 7.33 (s, 1H), 7.19 (s, 1H), 5.09 (s, 2H), 4.59 (s, 2H), 4.48(q, 2H), 3.68 (s, 2H), 1.42 (t, 3H)

Example 118.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 43.6%) was prepared in the samefashion as Example 100, except that in Step 1, 30 mg ofN-(2-methoxyethyl)-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-aminewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.49 (s, 2H), 7.94 (s, 1H), 7.14 (d, 1H), 5.50 (s, 4H), 5.05 (s, 2H),4.55 (s, 2H), 3.38-3.28 (m, 7H)

Example 119.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

48 mg of the title compound (yield: 51.6%) was prepared in the samefashion as Example 100, except that in Step 1, 62 mg of1-ethylpyrazole-4-boronic acid pinacol ester was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.96 (s, 1H), 7.89(s, 1H), 7.66 (s, 1H), 7.06 (s, 1H), 7.01 (s, 1H), 5.02 (s, 2H), 4.58(s, 2H), 4.18 (q, 2H), 3.67 (s, 2H), 1.47 (t, 3H)

Example 120.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-chloro-3-methyl-imidazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

17 mg of the title compound (yield: 24.9%) was prepared in the samefashion as Example 100, except that in Step 1, 42 mg of2-chloro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazolewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.98 (s, 1H), 7.20 (S, 1H), 7.14 (d, 1H), 7.05 (s, 1H), 5.09 (s, 2H),4.57 (s, 2H), 3.68 (s, 2H), 3.65 (s, 3H)

Example 121.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-pyridin-2-onetrifluoroacetate

8 mg of the title compound (yield: 11.8%) was prepared in the samefashion as Example 100, except that in Step 1, 40 mg of1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.97 (s, 2H), 7.77 (d, 1H), 7.12 (d, 2H), 6.58 (d, 1H), 5.04 (s, 2H),4.59 (s, 2H), 3.68 (s, 2H), 3.60 (s, 3H)

Example 122.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-ethyl-pyridin-2-onetrifluoroacetate

46 mg of the title compound (yield: 52.4%) was prepared in the samefashion as Example 100, except that in Step 1, 70 mg of1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was usedinstead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.98 (s,2H), 7.77 (d, 1H), 7.13 (d, 2H), 6.59 (d, 1H), 5.05 (s, 2H), 4.59 (s,2H), 4.08 (q, 2H), 3.68 (s, 2H), 1.36 (t, 3H)

Example 123.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-isopropyl-pyridin-2-onetrifluoroacetate

14 mg of the title compound (yield: 33.3%) was prepared in the samefashion as Example 100, except that in Step 1, 27 mg of1-isopropyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester wasused instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.98(s, 1H), 7.86 (s, 1H), 7.74 (d, 1H), 7.15 (d, 2H), 6.60 (d, 1H), 5.20(m, 1H), 5.06 (s, 2H), 4.59 (s, 2H), 3.67 (s, 2H), 1.44 (d, 6H)

Example 124.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

14 mg of the title compound (yield: 27.3%) was prepared in the samefashion as Example 100, except that in Step 1, 31 mg of1-methyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridinewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.95 (s, 1H), 7.06 (s, 2H), 6.08 (s, 1H), 5.02 (s, 2H), 4.58 (s, 2H),3.85 (s, 2H), 3.67 (s, 2H), 3.59 (s, 2H), 2.96 (s, 3H), 2.86 (s, 2H)

Example 125.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

11 mg of the title compound (yield: 18.2%) was prepared in the samefashion as Example 100, except that in Step 1, 35 mg of1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-yl)ethanonewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.94 (s, 1H), 7.03 (s, 1H), 6.95 (d, 1H), 6.09 (s, 1H), 5.00 (s, 2H),4.58 (s, 2H), 4.16 (d, 2H), 3.75 (d, 2H), 3.66 (s, 2H), 2.56 (d, 2H),2.15 (s, 3H)

Example 126.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

42 mg of the title compound (yield: 90.9%) was prepared in the samefashion as Example 100, except that in Step 1, 21 mg of3,4-(methylenedioxy)phenyl boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.96 (s, 1H), 7.11(s, 1H), 7.06 (s, 3H), 6.81 (d, 1H), 5.97 (s, 2H), 5.02 (s, 2H), 4.58(s, 2H), 3.67 (s, 2H).

Example 127.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-indazol-6-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

27 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 100, except that in Step 1, 34 mg of1H-indazole-6-boronic acid pinacol ester was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.02 (d, 2H), 7.78(d, 1H), 7.73 (s, 1H), 7.42 (d, 1H), 7.36 (s, 1H), 7.16 (s, 1H), 5.08(s, 2H), 4.60 (s, 2H), 3.68 (s, 2H)

Example 128.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-([1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

40 mg of the title compound (yield: 90.9%) was prepared in the samefashion as Example 100, except that in Step 1, 34 mg of7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridinewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.74 (d, 1H), 8.40 (s, 1H), 8.03 (s, 1H), 7.87 (s, 1H), 7.57 (s, 1H),7.47 (d, 1H), 7.21 (s, 1H), 5.12 (s, 2H), 4.60 (s, 2H), 3.69 (s, 2H)

Example 129.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2,1,3-benzoxadiazol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

34 mg of the title compound (yield: 72.7%) was prepared in the samefashion as Example 100, except that in Step 1, 26 mg ofbenzo[c][1,2,5]oxadiazole-5-boronic acid pinacol ester was used insteadof 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.02 (d, 2H),7.94 (d, 1H), 7.86 (d, 1H), 7.57 (d, 1H), 7.21 (d, 1H), 5.12 (s, 2H),4.60 (s, 2H), 3.67 (s, 2H)

Example 130.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-7-fluoro-indolin-2-onetrifluoroacetate

14 mg of the title compound (yield: 27.3%) was prepared in the samefashion as Example 100, except that in Step 1,7-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one 39mg was used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz)δ 7.98 (s, 1H), 7.35 (s, 1H), 7.29 (d, 1H), 7.22 (s, 1H), 7.11 (s, 1H),5.05 (s, 2H), 4.58 (s, 2H), 3.65 (d, 2H), 3.59 (s, 2H)

Example 131.N-[6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,3-benzothiazol-2-yl]acetamidetrifluoroacetate

28 mg of the title compound (yield: 54.5%) was prepared in the samefashion as Example 100, except that in Step 1, 44 mg ofN-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamidewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.07 (s, 1H), 8.00 (s, 1H), 7.71 (d, 1H), 7.64 (d, 1H), 7.30 (d, 1H),7.14 (d, 1H), 5.07 (s, 2H), 4.60 (s, 2H), 3.68 (s, 2H), 2.27 (s, 3H)

Example 132.7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-2H-isoquinolin-1-onetrifluoroacetate

33 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 100, except that in Step 1, 38 mg of(1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)boronic acid pinacol ester wasused instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.14(s, 1H), 8.00 (s, 1H), 7.74 (d, 1H), 7.35 (d, 1H), 7.34 (s, 1H), 7.15(s, 1H), 5.08 (s, 2H), 4.59 (s, 2H), 3.65 (s, 2H), 3.53 (t, 2H), 3.01(t, 2H)

Example 133.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

26 mg of the title compound (yield: 54.5%) was prepared in the samefashion as Example 100, except that in Step 1, 38 mg of6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.98 (s, 1H), 7.43 (s, 1H), 7.40 (d, 1H), 7.20 (d, 1H), 7.10 (d, 1H),6.87 (d, 1H), 5.05 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H), 2.98 (t, 2H),2.58 (t, 2H)

Example 134.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

34 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 100, except that in Step 1, 37 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.98 (s, 1H), 7.26 (s, 2H), 7.17 (s, 1H), 7.09 (s, 1H), 5.04 (s, 2H),4.59 (s, 2H), 3.68 (s, 2H), 2.94 (t, 2H), 2.55 (t, 2H), 2.27 (s, 3H)

Example 135.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-1H-quinolin-2-onetrifluoroacetate

33 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 100, except that in Step 1, 40 mg of8-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-quinolin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.01 (s, 1H), 7.90 (d, 1H), 7.61 (d, 2H), 7.25 (s, 1H), 7.12 (s, 1H),6.59 (d, 1H), 5.07 (s, 2H), 4.60 (s, 2H), 3.69 (s, 2H), 2.47 (s, 3H)

Example 136.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

29 mg of the title compound (yield: 54.5%) was prepared in the samefashion as Example 100, except that in Step 1, 41 mg of8-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.98 (s, 1H), 7.26-7.24 (m, 3H), 7.11 (s, 1H), 5.05 (s, 2H), 4.59 (s,2H), 3.68 (s, 2H), 3.01 (t, 2H), 2.60 (t, 2H)

Example 137.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-1H-quinolin-2-onetrifluoroacetate

30 mg of the title compound (yield: 54.5%) was prepared in the samefashion as Example 100, except that in Step 1, 40 mg of8-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-quinolin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.01 (s, 1H), 7.95 (d, 1H), 7.65 (s, 1H), 7.60 (d, 1H), 7.31 (s, 1H),7.13 (s, 1H), 6.65 (d, 1H), 5.08 (s, 2H), 4.60 (s, 2H), 3.68 (s, 2H)

Example 138.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

41 mg of the title compound (yield: 81.8%) was prepared in the samefashion as Example 100, except that in Step 1, 37 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400MHz) δ 7.99 (s, 1H), 7.48 (d, 1H), 7.44 (s, 1H), 7.22 (s, 1H), 7.12 (s,2H), 5.05 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H), 3.34 (s, 3H), 2.93 (t,2H), 2.62 (t, 2H)

Example 139.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 100, except that in Step 1, 38 mg of(5-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)boronic acid pinacolester was used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400MHz) δ 7.98 (s, 1H), 7.09 (d, 1H), 6.78 (d, 1H), 6.58 (s, 2H), 5.05 (s,2H), 4.59 (s, 2H), 4.17 (t, 2H), 3.68 (s, 2H), 3.43 (t, 2H), 2.10 (s,3H).

Example 140.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

27 mg of the title compound (yield: 54.5%) was prepared in the samefashion as Example 100, except that in Step 1, 38 mg of4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazinewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.95 (s, 1H), 7.04 (s, 3H), 6.91 (s, 1H), 6.68 (d, 1H), 5.01 (s, 2H),4.58 (s, 2H), 4.27 (s, 2H), 3.66 (s, 2H), 3.36-3.27 (m, 6H), 2.90 (s,3H)

Example 141.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4H-1,4-benzoxazin-3-onetrifluoroacetate

11 mg of the title compound (yield: 27.3%) was prepared in the samefashion as Example 100, except that in Step 1, 30 mg of6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-benzo[b][1,4]oxazine-3(4H)-oneswas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.97 (s, 1H), 7.21-7.12 (m, 4H), 6.96 (d, 1H), 5.05 (s, 2H), 4.59 (d,4H), 3.59 (s, 2H)

Example 142.7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2-onetrifluoroacetate

35 mg of the title compound (yield: 72.7%) was prepared in the samefashion as Example 100, except that in Step 1, 41 mg of7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.99 (s, 1H), 7.28 (s, 1H), 7.26 (d, 1H), 7.18 (d, 1H), 7.13 (d, 1H),7.09 (s, 1H), 5.31 (s, 2H), 5.06 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H)

Example 143.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2-onetrifluoroacetate

31 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 100, except that in Step 1, 38 mg of6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.98 (s, 1H), 7.49 (d, 1H), 7.43 (s, 1H), 7.21 (d, 1H), 7.11 (d, 1H),6.89 (d, 1H), 5.33 (s, 2H), 5.05 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H)

Example 144.7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4-methyl-1,4-benzoxazin-3-onetrifluoroacetate

34 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 100, except that in Step 1, 43 mg of4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzo[b][1,4]oxazine-7-boronic acidpinacol ester was used instead of 4-acetylphenylboronicacid. ¹H-NMR(MeOD, 400 MHz) δ 7.98 (s, 1H), 7.28 (d, 1H), 7.20 (d, 2H), 7.12 (d,2H), 5.05 (s, 2H), 4.62 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H), 3.34 (s,3H)

Example 145.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

6 mg of the title compound (yield: 18.2%) was prepared in the samefashion as Example 100, except that in Step 1, 36 mg of(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)boronic acid pinacol ester wasused instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.97(s, 1H), 7.92 (s, 1H), 7.69 (s, 1H), 7.17 (s, 1H), 7.12 (s, 1H), 5.05(s, 2H), 4.58 (s, 2H), 3.67 (s, 2H), 3.50 (d, 2H), 2.86 (m, 2H), 1.95(m, 2H)

Example 146. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one trifluoroacetate

83 mg of the title compound (yield: 87.0%) was prepared in the samefashion as Example 100, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 60 mg of4-(methanesulfonyl)phenylboronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.02-7.97 (m, 3H),7.92-7.86 (m, 3H), 7.62 (s, 1H), 5.12 (s, 2H), 4.59 (s, 2H), 3.68 (s,2H), 3.15 (s, 3H)

Example 147.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

45 mg of the title compound (yield: 56.3%) was prepared in the samefashion as Example 100, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 83 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.99 (s, 1H), 7.58-7.48 (m, 4H), 7.06 (d, 2H), 5.08 (s, 2H), 4.59 (s,2H), 3.67 (s, 2H), 3.45-3.32 (m, 8H)

Example 148.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

33 mg of the title compound (yield: 35.6%) was prepared in the samefashion as Example 100, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 59 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 9.01 (s,1H), 8.29 (d, 1H), 8.02 (s, 1H), 7.97 (s, 1H), 7.85 (d, 1H), 7.66 (s,1H), 5.13 (s, 2H), 4.59 (s, 2H), 3.67 (s, 2H)

Example 149.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 40.0%) was prepared in the samefashion as Example 100, except that in Step 1, X mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 53 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.20-8.17 (m, 2H),8.00 (s, 1H), 7.68 (s, 1H), 7.51 (s, 1H), 7.16 (d, 1H), 5.10 (s, 2H),4.59 (s, 2H), 3.72 (s, 2H), 3.27 (s, 6H)

Example 150.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

40 mg of the title compound (yield: 45.8%) was prepared in the samefashion as Example 100, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 44 mg of 3,4-(methylenedioxy)phenylboronic acid was used instead of 4-acetylphenylboronicacid. ¹H-NMR(MeOD, 400 MHz) δ 7.98 (s, 1H), 7.45 (d, 2H), 7.11 (d, 2H), 6.93 (s,1H), 6.84 (d, 1H), 5.96 (s, 2H), 5.07 (s, 2H), 4.58 (s, 2H), 3.66 (s,2H)

Example 151.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

36 mg of the title compound (yield: 37.6%) was prepared in the samefashion as Example 100, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 62 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-acetylphenylboronicacid. MS (ESI) m/z=444.1 (M+H)+

Example 152.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

40 mg of the title compound (yield: 41.8%) was prepared in the samefashion as Example 100, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 62 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400MHz) δ 8.00 (s, 1H), 7.57-7.50 (m, 4H), 7.14 (d, 1H), 5.09 (s, 2H), 4.59(s, 2H), 3.68 (s, 2H), 3.35 (s, 3H), 2.95 (t, 2H), 2.63 (t, 2H)

Example 153.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

37 mg of the title compound (yield: 45.2%) was prepared in the samefashion as Example 100, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 48 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-acetylphenylboronicacid. ¹H-NMR(MeOD, 400 MHz) δ 7.97 (s, 1H), 7.91 (s, 1H), 7.73 (s, 1H), 7.36 (d,2H), 5.05 (s, 2H), 4.58 (s, 2H), 4.18 (q, 2H), 3.67 (s, 2H), 1.47 (t,3H)

Example 154.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 43.3%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 43 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 21 mg of4-(methanesulfonyl)phenylboronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.99-7.92 (m, 3H),7.81 (d, 2H), 7.38 (s, 1H), 5.03 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H),3.12 (s, 3H), 2.34 (s, 3H)

Example 155.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

6 mg of the title compound (yield: 13.5%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 43 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 40 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.90 (s, 1H), 7.51 (d, 2H), 7.06-7.02 (m, 3H), 4.98 (s, 2H), 4.58 (s,2H), 3.67 (s, 2H), 3.45 (t, 4H), 3.38 (t, 4H), 2.30 (s, 3H)

Example 156.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

14 mg of the title compound (yield: 30.8%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 43 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 28 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.92 (s,1H), 8.19 (d, 1H), 7.97 (s, 1H), 7.81 (d, 1H), 7.45 (s, 1H), 5.06 (s,2H), 4.59 (s, 2H), 3.68 (s, 2H), 2.35 (s, 3H)

Example 157.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

17 mg of the title compound (yield: 38.5%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 43 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 26 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.11-8.07 (m, 2H),7.92 (s, 1H), 7.18-7.14 (m, 2H), 5.10 (s, 2H), 4.58 (s, 2H), 3.68 (s,2H), 3.27 (s, 6H), 2.32 (s, 3H)

Example 158.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

28 mg of the title compound (yield: 62.5%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 43 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 26 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.89(s, 1H), 7.05-7.00 (m, 2H), 6.80 (d, 1H), 5.95 (s, 2H), 4.96 (s, 2H),4.58 (s, 2H), 3.67 (s, 2H), 2.29 (s, 3H)

Example 159.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

10 mg of the title compound (yield: 24.0%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 43 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 23 mg of 1-ethylpyrazole-4-boronicacid pinacol ester was used instead of 4-acetylphenylboronicacid. ¹H-NMR(MeOD, 400 MHz) δ 7.88 (s, 1H), 7.86 (s, 1H), 7.64 (s, 1H), 6.91 (s,1H), 4.96 (s, 2H), 4.58 (s, 2H), 4.18 (q, 2H), 3.67 (s, 2H), 2.28 (s,3H), 1.46 (t, 3H)

Example 160.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate Step 1: tert-butylN-[3,3-difluoro-2-[[4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamate

60 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31, 10 mg of4-ethynyl-1-methyl-1H-pyrazole, 8 mg oftetrakis(triphenylphosphine)palladium (Pd(PPh₃)₄), and 3 mg of copper(I)iodide (CuI) were dissolved in 1 mL of N,N-dimethylformamide, followedby the addition of 56.0 uL of triethylamine, and the resulting solutionwas stirred overnight at 90° C. The resulting reaction mixture wasfiltered through a celite pad and concentrated under reduced pressure togive a residue. The residue thus obtained was dissolved in ethylacetate,washed with distilled water, dried over anhydrous magnesium sulfate, andconcentrated under reduced pressure to give a yellow liquid residue. Theresidue was purified with silica gel column chromatography (developingsolvent: n-hexane/ethyl acetate=2/1) to give 51.7 mg of the titlecompound as a yellow liquid (yield: 82.1%). MS (ESI) m/z=372.0 (M+H)+

Step 2:2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one

51.7 mg of tert-butylN-[3,3-difluoro-2-[[4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamateprepared in Step 1 was dissolved in 1.0 mL of dichloromethane, followedby the addition of 0.1 mL of trifluoroacetic acid, and the resultingsolution was stirred at room temperature for 2 hours. The reactionmixture thus obtained was concentrated, followed by the addition ofdichloromethane. The solution was concentrated under reduced pressureand then dried in vacuo to obtain a yellow liquid residue. The residuewas purified with silica gel column chromatography (developing solvent:dichloromethane/methanol=10/1) to give 10 mg of the title compound as awhite solid (yield: 24.5%). ¹H-NMR (MeOD, 400 MHz) δ 8.62 (s, 1H), 8.19(d, 1H), 7.94 (s, 2H), 7.70 (s, 1H), 7.48 (d, 1H), 4.61 (s, 2H), 3.92(s, 3H), 3.40 (s, 2H)

Example 161.7-[(E)-2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]vinyl]-1H-pyrido[2,3-b][1,4]oxazin-2-onetrifluoroacetate

17 mg of the title compound (yield: 36.4%) was prepared in the samefashion as Example 100, except that in Step 1, 42 mg of7-[(E)-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl]-1H,2H,3H-pyrido[2,3,b][1,4]oxazin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.97 (s, 1H), 7.87 (s, 1H), 7.44 (s, 1H), 7.23 (d, 1H), 7.04 (d, 2H),6.85 (d, 1H), 5.04 (s, 2H), 4.84 (s, 2H), 4.58 (s, 2H), 3.60 (s, 2H)

Example 162.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 54.5%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 39 mg of5-ethynyl-N,N-dimethylpyridine-2-amine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.15 (s, 1H),7.98 (s, 1H), 7.73 (d, 1H), 7.17 (s, 1H), 7.08 (s, 1H), 6.90 (d, 1H),5.05 (s, 2H), 4.59 (s, 2H), 3.68 (s, 2H), 3.20 (s, 6H)

Example 163.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

42 mg of the title compound (yield: 81.8%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 51 mg of4-(5-ethynylpyridin-2-yl)morpholine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.23 (s, 1H),7.98 (s, 1H), 7.61 (d, 1H), 7.13 (s, 1H), 7.07 (s, 1H), 6.79 (d, 1H),5.04 (s, 2H), 4.59 (s, 2H), 3.78 (s, 4H), 3.67 (s, 2H), 3.56 (s, 4H)

Example 164.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

26 mg of the title compound (yield: 81.8%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 70 mg oftert-butyl-6-ethynyl-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate was usedinstead of 4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 7.97(s, 1H), 7.07 (d, 2H), 6.72 (s, 1H), 6.67 (t, 2H), 5.03 (s, 2H), 4.58(s, 2H), 4.21 (s, 2H), 3.67 (s, 2H), 3.34-3.31 (s, 2H)

Example 165.6-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

38 mg of the title compound (yield: 72.7%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 46 mg of6-ethynyl-1,2,3,4-tetrahydroquinolin-2-one was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H),7.30 (d, 2H), 7.14 (s, 1H), 7.07 (s, 1H), 6.86 (d, 1H), 5.04 (s, 2H),4.59 (s, 2H), 3.67 (s, 2H), 2.96 (t, 2H), 2.58 (t, 2H)

Example 166.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

38 mg of the title compound (yield: 81.8%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 43 mg of7-ethynyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H),7.52 (s, 1H), 7.16 (s, 1H), 7.07 (s, 1H), 7.01 (s, 1H), 5.05 (s, 2H),4.59 (s, 2H), 4.39 (s, 2H), 3.67 (s, 2H), 3.38 (s, 2H)

Example 167.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

39 mg of the title compound (yield: 72.7%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamatewas used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 43 mg of7-ethynyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H),7.69 (s, 1H), 7.12 (s, 1H), 7.05 (d, 2H), 5.04 (s, 2H), 4.58 (s, 2H),4.18 (s, 2H), 3.67 (s, 2H), 3.55 (s, 2H)

Example 168.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

26 mg of the title compound (yield: 54.5%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 43 mg of6-ethynyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H),7.16 (s, 1H), 7.07 (s, 1H), 7.01 (d, 1H), 6.91 (d, 1H), 5.04 (s, 2H),4.58 (s, 2H), 4.36 (s, 2H), 3.66 (s, 2H), 3.41 (s, 2H)

Example 169.7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-1H-pyrido[2,3-b][1,4]oxazin-2-onetrifluoroacetate

32 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 47 mg of7-ethynyl-1H,2H,3H-pyrido[2,3-b][1,4]oxazin-2-one was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 7.98 (s, 1H),7.93 (s, 1H), 7.32 (s, 1H), 7.21 (s, 1H), 7.10 (s, 1H), 5.06 (s, 2H),4.87 (s, 2H), 4.59 (s, 2H), 3.67 (s, 2H)

Example 170.7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-4H-pyrido[3,2-b][1,4]oxazin-3-onetrifluoroacetate

34 mg of the title compound (yield: 63.6%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 and 47 mg of7-ethynyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.03 (s, 1H),7.98 (s, 1H), 7.37 (s, 1H), 7.20 (s, 1H), 7.09 (s, 1H), 5.06 (s, 2H),4.68 (s, 2H), 4.59 (s, 2H), 3.67 (s, 2H)

Example 171.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 72.7%) was prepared in the samefashion as Example 160, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 was used instead of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31. ¹H-NMR (MeOD, 400 MHz) δ 7.97 (s, 1H),7.84 (s, 1H), 7.61 (s, 1H), 7.08 (d, 2H), 5.04 (s, 2H), 4.58 (s, 2H),3.90 (s, 3H), 3.67 (s, 2H)

Example 172.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(2-thienyl)ethyl]-1,2,4-triazol-3-onetrifluoroacetate

43 mg of tert-butylN-[3,3-difluoro-2-[[5-oxo-4-[2-(2-thienyl)ethyl]-1,2,4-triazol-1-yl]methyl]allyl]carbamateprepared in Reference Example 44 was dissolved in 5.0 mL ofdichloromethane, followed by the addition of 0.5 mL of trifluoroacetate,and the resulting solution was stirred at room temperature for 3 hours.The reaction mixture thus obtained was concentrated, followed by theaddition of dichloromethane. The concentrated reaction mixture waswashed with an aqueous solution of sodium hydrogen carbonate, then driedover anhydrous magnesium sulfate, and concentrated under reducedpressure to obtain a yellow liquid residue. The residue was purifiedwith silica gel column chromatography (developing solvent:dichloromethane/methanol=10/1) to give 34 mg of the title compound as awhite solid (yield: 100%). ¹H-NMR (MeOD, 400 MHz) δ 7.67 (s, 1H), 7.25(s, 1H), 6.94 (s, 1H), 6.86 (s, 1H), 4.55 (s, 2H), 3.96 (t, 2H), 3.63(s, 2H), 3.27 (t, 2H)

Example 173. 2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]-1,2,4-triazol-3-one trifluoroacetateStep 1: tert-butylN-[3,3-difluoro-2-[[4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamate

60 mg of tert-butylN-[2-[[4-(5-bromo-2-thienyl)ethyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 45 and 32 mg of4-(methanesulfonyl)phenylboronic acid were dissolved in 1.6 mL of1,4-dioxane, followed by the addition of 0.4 mL of 1 M potassiumcarbonate and 3 mg ofpalladiumdi[1,1′-bis(diphenylphospino)ferrocene]dichloride(PdCl₂(dppf)), and the resulting solution was stirred overnight at 90°C. The resulting reaction mixture was filtered through a celite pad andconcentrated under reduced pressure to give a residue. The residue thusobtained was dissolved in ethylacetate, washed with distilled water,dried over anhydrous magnesium sulfate, and concentrated under reducedpressure to give a yellow liquid residue. The residue was purified withsilica gel column chromatography (developing solvent: n-hexane/ethylacetate=1/2) to give 48 mg of the title compound (yield: 69.2%). MS(ESI) m/z=455.2 (M+H)+

Step 2:2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]-1,2,4-triazol-3-one

48 mg of tert-butylN-[3,3-difluoro-2-[[4-[2-[5-(4-methylsulfonylphenyl)-2-thienyl]ethyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamateprepared in Step 1 was dissolved in 1.0 mL of dichloromethane, followedby the addition of 0.1 mL of trifluoroacetic acid, and the resultingsolution was stirred at room temperature for 2 hours. The reactionmixture thus obtained was concentrated, followed by the addition ofdichloromethane. The solution was concentrated under reduced pressureand then dried in vacuo to obtain a yellow liquid residue. The residuewas purified with silica gel column chromatography (developing solvent:dichloromethane/methanol=10/1) to give 34 mg of the title compound(yield: 59.2%). ¹H-NMR (MeOD, 400 MHz) δ 7.94-7.92 (m, 2H), 7.82-7.77(m, 3H), 7.44 (s, 1H), 6.92 (s, 1H), 4.56 (s, 2H), 3.99 (t, 2H), 3.65(s, 2H), 3.36 (s, 3H), 3.31 (t, 2H)

Example 174.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-piperazin-1-ylphenyl)-2-thienyl]ethyl]-1,2,4-triazol-3-oneditrifluoroacetate

9 mg of the title compound (yield: 16.0%) was prepared in the samefashion as Example 173, except that in Step 1, 49 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 7.74 (s, 1H), 7.50 (d, 1H), 7.10 (s, 1H), 7.03 (d, 1H), 6.80(s, 1H), 4.56 (s, 2H), 3.98 (t, 2H), 3.59 (s, 2H), 3.44 (t, 4H), 3.37(t, 4H), 3.24 (t, 2H)

Example 175.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 37.6%) was prepared in the samefashion as Example 173, except that in Step 1, 34 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.92 (s, 1H), 8.19 (d, 1H), 7.82 (d, 1H), 7.79 (s, 1H), 7.51 (s, 1H),6.97 (s, 1H), 4.56 (s, 2H), 4.01 (t, 2H), 3.65 (s, 2H), 3.36 (s, 3H),3.32 (t, 2H)

Example 176.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 35.2%) was prepared in the samefashion as Example 173, except that in Step 1, 31 mg of6-(dimethylamino)pyridine-3-boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.10 (s,1H), 8.06 (d, 1H), 7.76 (s, 1H), 7.22 (s, 1H), 7.13 (d, 1H), 6.87 (s,1H), 4.56 (s, 2H), 3.99 (t, 2H), 3.65 (s, 2H), 3.36 (t, 2H), 3.27 (s,6H)

Example 177.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1,3-benzodioxol-5-yl)-2-thienyl]ethyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 55.2%) was prepared in the samefashion as Example 173, except that in Step 1, 34 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 7.73 (s, 1H), 7.06-7.02 (m, 3H), 6.82-6.77 (m, 2H), 5.97 (s, 2H),4.59 (s, 2H), 3.97 (t, 2H), 3.63 (s, 2H), 3.23 (t, 2H)

Example 178.6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

21 mg of the title compound (yield: 36.0%) was prepared in the samefashion as Example 173, except that in Step 1, 36 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 7.75 (s, 1H), 7.24 (d, 1H), 7.13 (d, 1H), 6.80 (d, 1H), 4.56(s, 2H), 3.97 (t, 2H), 3.63 (s, 2H), 3.24 (t, 2H), 2.94 (t, 2H), 2.57(t, 2H), 2.27 (s, 3H).

Example 179.6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

17 mg of the title compound (yield: 30.4%) was prepared in the samefashion as Example 173, except that in Step 1, 36 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 7.75 (s, 1H), 7.47 (d, 1H), 7.43 (s, 1H), 7.18 (s,1H), 7.12 (d, 1H), 6.83 (s, 1H), 4.56 (s, 2H), 3.99 (t, 2H), 3.64 (s,2H), 3.32 (s, 3H), 3.26 (t, 2H), 2.94 (t, 2H), 2.64 (t, 2H)

Example 180.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1-ethylpyrazol-4-yl)-2-thienyl]ethyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 42.4%) was prepared in the samefashion as Example 173, except that in Step 1, 28 mg of1-ethylpyrazole-4-boronic acid pinacol ester was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.84 (s,1H), 7.72 (s, 1H), 7.63 (s, 1H), 6.95 (s, 1H), 6.75 (s, 1H), 4.56 (s,2H), 4.19 (q, 2H), 3.96 (t, 2H), 3.63 (s, 2H), 3.22 (t, 2H), 1.47 (t,3H)

Example 181.3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N,N-dimethyl-benzamidetrifluoroacetate

925 mg of the title compound (yield: 99.3%) was prepared in the samefashion as Example 100, except that in Step 1, 539 mg of3-(dimethylcarbamoyl)phenylboronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.00 (s, 1H), 7.70(d, 1H), 7.65 (s, 1H), 7.49 (t, 1H), 7.36 (d, 2H), 7.16 (d, 1H), 5.08(s, 2H), 4.59 (s, 2H), 3.67 (s, 2H), 3.13 (s, 3H), 3.03 (s, 3H)

Example 182.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3-methyl-1,4-dihydroquinazolin-2-onetrifluoroacetate

26 mg of the title compound (yield: 46.4%) was prepared in the samefashion as Example 100, except that in Step 1, 40 mg of3-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydroquinazolin-2-onewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ7.98 (s, 1H), 7.37 (d, 1H), 7.32 (s, 1H), 7.15 (d, 1H), 7.09 (d, 1H),6.78 (d, 1H), 5.04 (s, 2H), 4.59 (s, 2H), 4.48 (s, 2H), 3.67 (s, 2H),2.98 (s, 3H).

Example 183.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

26 mg of the title compound (yield: 60.7%) was prepared in the samefashion as Example 100, except that in Step 1, 26 mg of1-difluoromethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.31 (s, 1H), 7.95 (d, 2H), 7.49 (t, 1H), 7.13 (d, 2H), 5.05 (s, 2H),4.58 (s, 2H), 3.67 (s, 2H)

Example 184.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-isopropylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

36 mg of the title compound (yield: 81.8%) was prepared in the samefashion as Example 100, except that in Step 1, 17 mg of(1-isopropylpyrazole-4-yl)boronic acid was used instead of4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.94 (d, 2H), 7.67(s, 1H), 7.04 (m, 2H), 5.03 (s, 2H), 4.55 (m, 3H), 3.68 (s, 2H), 1.51(d, 6H)

Example 185.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

19 mg of the title compound (yield: 37.5%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg oftrimethyl-[2-[[3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2,4-triazole-1-yl]methoxy]ethyl]silanewas used instead of 4-acetylphenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ8.41 (bs, 1H), 8.21 (s, 1H), 8.02 (s, 1H), 7.96 (d, 1H), 7.70 (d, 1H),7.52 (t, 1H), 7.39 (d, 1H), 7.18 (d, 1H), 5.10 (s, 2H), 4.60 (s, 2H),3.68 (s, 2H)

Example 186.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3-methyl-1,4-dihydroquinazolin-2-onetrifluoroacetate

19 mg of the title compound (yield: 30.4%) was prepared in the samefashion as Example 100, except that in Step 1, 58 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 40 mg of3-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydroquinazolin-2-onewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.99 (s, 1H), 7.47 (d, 2H), 7.42 (d, 1H), 7.37 (s, 1H), 6.80 (d, 1H),5.07 (s, 2H), 4.59 (s, 2H), 4.50 (s, 2H), 3.67 (s, 2H), 2.83 (s, 3H)

Example 187.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-isopropyl-pyridin-2-onetrifluoroacetate

36 mg of the title compound (yield: 80.4%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 28 mg of1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-onewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.01 (s, 1H), 7.94 (d, 1H), 7.83 (dd, 1H), 7.56 (d, 1H), 7.48 (s, 1H),6.61 (d, 1H), 5.24 (m, 1H), 5.09 (s, 2H), 4.60 (s, 2H), 3.69 (s, 2H),1.46 (d, 6H)

Example 188.4-[[4-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-onetrifluoroacetate

28 mg of the title compound (yield: 53.3%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 27 mg of4-(4-acetyl-1-piperazinyl)phenylboronic acid was used instead of4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.99 (s, 1H), 7.54(d, 2H), 7.46 (d, 2H), 7.00 (d, 2H), 5.08 (s, 2H), 4.59 (s, 2H), 3.74(t, 2H), 3.68 (d, 4H), 3.24 (d, 2H), 3.18 (d, 2H), 2.15 (s, 3H)

Example 189.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-fluoro-1H-quinolin-2-onetrifluoroacetate

35 mg of the title compound (yield: 73.8%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 31 mg of8-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-quinolin-2-onewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.04 (s, 1H), 7.94 (d, 1H), 7.65 (m, 3H), 7.53 (s, 1H), 6.64 (d, 1H),5.11 (s, 2H), 4.61 (s, 2H), 3.70 (s, 2H)

Example 190.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-pyridin-2-onetrifluoroacetate

39 mg of the title compound (yield: 93.4%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 25 mg of(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)boronic acid pinacol ester wasused instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.02 (m, 2H), 7.87 (dd, 1H), 7.52 (d, 1H), 7.42 (s, 1H), 6.60 (d, 1H)5.08 (s, 2H), 4.60 (s, 2H), 3.68 (s, 2H), 3.62 (s, 3H)

Example 191.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1,4-dihydro-3,1-benzoxazin-2-onetrifluoroacetate

43 mg of the title compound (yield: 92.5%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 30 mg of1,4-dihydro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-3,1-benzoxazin-2-onewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.01 (s, 1H), 7.59 (d, 1H), 7.48 (s, 1H), 7.31 (dd, 1H), 7.19 (d, 1H),7.10 (s, 1H), 5.31 (s, 2H), 5.09 (s, 2H), 4.60 (s, 2H), 3.69 (s, 2H)

Example 192.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

25 mg of the title compound (yield: 54.2%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 29 mg of6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-onewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.00 (s, 1H), 7.53 (d, 1H), 7.46 (m, 3H), 6.89 (d, 1H), 5.08 (s, 2H),4.60 (s, 2H), 3.68 (s, 2H), 2.99 (t, 2H), 2.59 (t, 2H)

Example 193.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-ethyl-pyridin-2-onetrifluoroacetate

23 mg of the title compound (yield: 53.3%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 27 mg of1-ethyl-6-oxo-1,6-dihydropyridin-3-boronic acid pinacol ester was usedinstead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.03 (m,2H), 7.87 (dd, 1H), 7.54 (d, 1H), 7.44 (s, 1H), 6.61 (d, 1H), 5.09 (s,2H), 4.60 (s, 2H), 4.11 (q, 2H), 3.68 (s, 2H), 1.38 (t, 3H)

Example 194.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

24 mg of the title compound (yield: 56.1%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 17 mg of1-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.34 (s, 1H), 8.00 (d, 2H), 7.50 (m, 3H), 5.08 (s, 2H), 4.59 (s, 2H),3.68 (s, 2H)

Example 195.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-isopropylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

38 mg of the title compound (yield: 87.3%) was prepared in the samefashion as Example 100, except that in Step 1, 51 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 17 mg of(1-isopropylpyrazol-4-yl)boronic acid was used instead of4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.97 (d, 2H), 7.74(s, 1H), 7.37 (d, 2H), 5.06 (s, 2H), 4.56 (m, 3H), 3.68 (s, 2H), 1.52(d, 6H)

Example 196.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

8 mg of the title compound (yield: 15.2%) was prepared in the samefashion as Example 100, except that in Step 1, 52 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 50 mg oftrimethyl-[2-[[3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2,4-triazole-1-yl]methoxy]ethyl]silanewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.43 (bs, 1H), 8.24 (s, 1H), 8.04 (s, 1H), 7.95 (d, 1H), 7.76 (d, 1H),7.73 (s, 1H), 7.65 (s, 1H), 7.57 (t, 1H), 5.13 (s, 2H), 4.60 (s, 2H),3.68 (s, 2H)

Example 197.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate Step 1: tert-butyl N-[3,3-difluoro-2-[[4-[[6-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamate

40 mg of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 22 mg of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan weredissolved in 1.5 mL of 1,4-dioxane, followed by the addition of 0.2 mLof 1 M potassium carbonate and 2 mg ofpalladiumdi[1,1′-bis(diphenylphospino)ferrocene]dichloride(PdCl₂(dppf)), and the resulting solution was stirred overnight at 90°C. The resulting reaction mixture was filtered through a celite pad andconcentrated under reduced pressure to give a residue. The residue thusobtained was dissolved in ethylacetate, washed with distilled water,dried over anhydrous magnesium sulfate, and concentrated under reducedpressure to give a yellow liquid residue. The residue was purified withsilica gel column chromatography (developing solvent: n-hexane/ethylacetate=1/1) to give 38 mg of the title compound (yield: 83.8%). MS(ESI) m/z=491.2 (M+H)+

Step 2:2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one

47 mg of tert-butylN-[3,3-difluoro-2-[[4-[[6-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamateprepared in Step 1 was dissolved in 1.0 mL of dichloromethane, followedby the addition of 0.1 mL of trifluoroacetic acid, and the resultingsolution was stirred at room temperature for 2 hours. The reactionmixture thus obtained was concentrated, followed by the addition ofdichloromethane. Dichloromethane was added to the concentrated reactionmixture, and it was concentrated under reduced pressure to obtain ayellow liquid residue. The residue was purified with silica gel columnchromatography (developing solvent: dichloromethane/methanol=10/1) togive 4 mg of the title compound as a white solid (yield: 12.0%). ¹H-NMR(DMSO-d₆, 400 MHz) δ 8.40 (s, 1H), 8.22 (s, 1H), 8.02 (s, 4H), 7.97 (d,1H), 7.79 (dd, 1H), 7.46 (s, 1H), 5.15 (s, 2H), 4.53 (s, 2H), 3.49 (s,2H), 3.27 (s, 3H)

Example 198.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

30 mg of the title compound (yield: 76.9%) was prepared in the samefashion as Example 197, except that in Step 1, 30 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 8.03 (d, 2H), 7.82 (d, 1H), 7.62 (m, 3H), 7.39(s, 1H), 7.12 (d, 2H), 5.17 (s, 2H), 4.61 (s, 2H), 3.68 (s, 2H), 3.49(t, 4H), 3.40 (t, 4H)

Example 199.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-[6-(trifluoromethyl)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

37 mg of the title compound (yield: 98.5%) was prepared in the samefashion as Example 197, except that in Step 1, 21 mg of2-(trifluoromethyl)pyridine-5-boronic acid pinacol ester was usedinstead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 9.02 (s, 1H), 8.33 (dd, 1H), 8.24 (s, 1H), 8.05(s, 1H), 7.91 (dd, 2H), 7.73 (dd, 1H), 7.46 (s, 1H), 5.21 (s, 2H), 4.62(s, 2H), 3.70 (s, 2H)

Example 200.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

24 mg of the title compound (yield: 65.8%) was prepared in the samefashion as Example 197, except that in Step 1, 13 mg of(6-(dimethylamino)pyridin-3-yl)boronic acid was used instead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 8.24 (d, 2H), 8.11 (s, 1H), 8.04 (s, 1H), 7.89(d, 1H), 7.62 (dd, 1H), 7.43 (s, 1H), 7.18 (d, 1H), 5.20 (s, 2H), 4.61(s, 2H), 3.69 (s, 2H), 3.29 (s, 6H)

Example 201.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

30 mg of the title compound (yield: 83.5%) was prepared in the samefashion as Example 197, except that in Step 1, 20 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (DMSO-d₆, 400 MHz) δ 8.19 (d, 2H), 8.01 (bs, 2H), 7.85 (d, 1H),7.64 (dd, 1H), 7.40 (s, 1H), 7.32 (d, 1H), 7.21 (dd, 1H), 7.02 (d, 1H),6.07 (s, 2H), 5.12 (s, 2H), 4.52 (s, 2H), 3.48 (s, 2H)

Example 202.6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

36 mg of the title compound (yield: 92.4%) was prepared in the samefashion as Example 197, except that in Step 1, 23 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 8.03 (s, 1H), 7.98 (s, 1H), 7.79 (d, 1H), 7.57(dd, 1H), 7.38 (s, 1H), 7.32 (d, 2H), 5.17 (s, 2H), 4.62 (s, 2H), 3.69(s, 2H), 2.96 (t, 2H), 2.56 (t, 2H), 2.31 (s, 3H)

Example 203.6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

30 mg of the title compound (yield: 75.9%) was prepared in the samefashion as Example 197, except that in Step 1, 23 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-yl)boronic acid pinacolester was used instead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 8.03 (d, 1H), 7.81 (d, 1H), 7.61 (dd, 1H), 7.56(dd, 1H), 7.51 (s, 1H), 7.40 (s, 1H), 7.15 (d, 1H), 5.17 (s, 2H), 4.62(s, 2H), 3.69 (s, 2H), 3.33 (m, 3H), 2.95 (t, 2H), 2.62 (t, 2H).

Example 204.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1-ethylpyrazol-4-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

27 mg of the title compound (yield: 78.5%) was prepared in the samefashion as Example 197, except that in Step 1, 18 mg of1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole wasused instead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 8.07 (s, 1H), 8.02 (d, 2H), 7.89 (s, 1H), 7.76(d, 1H), 7.58 (dd, 1H), 7.36 (s, 1H), 5.15 (s, 2H), 4.61 (s, 2H), 4.23(q, 2H), 3.68 (s, 2H), 1.50 (t, 3H)

Example 205.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

36 mg of the title compound (yield: 91.4%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57. ¹H-NMR (MeOD, 400 MHz) δ 8.10 (s, 1H),8.03 (d, 3H), 7.93 (m, 3H), 7.68 (d, 1H), 7.48 (s, 1H), 5.20 (s, 2H),4.62 (s, 2H), 3.69 (s, 2H), 3.17 (s, 3H)

Example 206.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

18 mg of the title compound (yield: 44.4%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 31 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan. ¹H-NMR (MeOD, 400 MHz) δ 7.99 (d,2H), 7.87 (d, 1H), 7.62 (m, 3H), 7.44 (s, 1H), 7.14 (s, 1H), 5.19 (s,2H), 4.61 (s, 2H), 3.68 (s, 2H), 3.48 (d, 4H), 3.42 (d, 4H), 3.32 (s,3H)

Example 207.5-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-ethyl-pyridin-2-onetrifluoroacetate

32 mg of the title compound (yield: 86.4%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 20 mg of1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was usedinstead of 4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan. ¹H-NMR (MeOD, 400 MHz) δ 8.03 (d,2H), 7.91 (m, 3H), 7.54 (d, 1H), 7.44 (s, 1H), 6.66 (d, 1H), 5.19 (s,2H), 4.61 (s, 2H), 4.13 (q, 2H), 3.69 (s, 2H), 1.40 (t, 3H)

Example 208.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 94.6%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 20 mg of6-(dimethylamino)pyridine-3-boronic acid pinacol ester was used insteadof 4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 8.30 (d, 1H), 8.21 (s, 1H), 8.04 (s, 2H), 7.96(d, 1H), 7.60 (d, 1H), 7.48 (s, 1H), 7.27 (d, 1H), 5.20 (s, 2H), 4.61(s, 2H), 3.70 (s, 2H), 3.32 (s, 6H)

Example 209.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

31 mg of the title compound (yield: 82.7%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 20 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan. ¹H-NMR (MeOD, 400 MHz) δ 8.02 (s,1H), 7.92 (s, 1H), 7.84 (d, 1H), 7.54 (d, 1H), 7.42 (s, 1H), 7.14 (d,2H), 7.91 (d, 1H), 6.00 (s, 2H), 5.17 (s, 2H), 4.61 (s, 2H), 3.68 (s,2H)

Example 210.6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

29 mg of the title compound (yield: 71.6%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 23 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan. ¹H-NMR (MeOD, 400 MHz) δ 8.03 (s,1H), 7.94 (s, 1H), 7.85 (d, 1H), 7.57 (d, 1H), 7.42 (s, 1H), 7.34 (d,2H), 5.18 (s, 2H), 4.61 (s, 2H), 3.69 (s, 2H), 2.98 (t, 2H), 2.58 (t,2H), 2.33 (s, 3H)

Example 211.6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

27 mg of the title compound (yield: 66.7%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 23 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-yl)boronic acid pinacolester was used instead of4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan.¹H-NMR (MeOD, 400 MHz) δ 8.02 (d, 2H), 7.87 (d, 1H), 7.58 (m, 3H), 7.44(s, 1H), 7.19 (d, 1H), 5.18 (s, 2H), 4.62 (s, 2H), 3.69 (s, 2H), 3.38(s, 3H), 2.98 (t, 2H), 2.65 (t, 2H)

Example 212.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 72.8%) was prepared in the samefashion as Example 197, except that in Step 1, 42 mg of tert-butylN-[2-[[4-[(5-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 58 was used instead of tert-butylN-[2-[[4-[(6-bromobenzothiophen-2-yl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 57 and 18 mg of1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole wasused instead of 4,4,5,5-tetramethyl-2-(4-methylsulfonylphenyl)-1,3,2-dioxaborolan. ¹H-NMR (MeOD, 400 MHz) δ 8.04 (d,2H), 7.97 (s, 1H), 7.88 (s, 1H), 7.81 (d, 1H), 7.57 (d, 1H), 7.39 (s,1H), 5.17 (s, 2H), 4.61 (s, 2H), 4.24 (q, 2H), 3.68 (s, 2H), 1.51 (t,3H)

Example 213.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-piperazin-1-yl-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

28 mg of the title compound (yield: 56.2%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 57 mg of tert-butyl4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.93 (s, 1H), 8.80 (s, 1H), 8.35 (d, 1H), 8.12 (d, 1H), 7.98(t, 1H), 7.81 (d, 1H), 7.03 (d, 1H), 4.68 (s, 2H), 3.93 (s, 4H), 3.75(s, 2H), 3.36 (s, 4H)

Example 214.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[4-(morpholine-4-carbonyl)phenyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

28 mg of the title compound (yield: 53.6%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 46 mg of4-(morpholine-4-carbonyl)phenylboronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.84 (s, 1H), 8.23 (t, 3H), 8.06 (t, 1H), 7.94 (d, 1H), 7.57 (d, 2H),4.68 (s, 2H), 3.76-3.66 (m, 8H), 3.51 (bs, 2H)

Example 215.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-morpholino-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

34 mg of the title compound (yield: 70.5%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 42 mg of6-(morpholin-4-yl)pyridine-3-boronic acid pinacol ester was used insteadof 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.81(d, 2H), 8.40 (d, 1H), 8.13 (d, 1H), 7.99 (t, 1H), 7.79 (d, 1H), 7.05(d, 1H), 4.68 (s, 2H), 3.84 (s, 4H), 3.76 (s, 2H), 3.64 (s, 4H)

Example 216.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(3-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

36 mg of the title compound (yield: 74.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 56 mg of3-[4-N-Boc-piperazin-1-yl]phenylboronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.81 (s, 1H), 8.17 (d, 1H), 8.02 (t, 1H), 7.88 (d, 1H), 7.75 (s, 1H),7.66 (d, 1H), 7.43 (t, 1H), 7.14 (d, 1H), 4.68 (s, 2H), 3.76 (s, 2H),3.52 (d, 4H), 3.43 (d, 4H)

Example 217.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[3-(dimethylamino)-4-fluoro-phenyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

30 mg of the title compound (yield: 62.5%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 27 mg of(3-(dimethylamino)-4-fluorophenyl)boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.75 (s,1H), 8.13 (d, 1H), 7.99 (t, 1H), 7.83 (d, 1H), 7.70 (d, 1H), 7.66-7.64(m, 1H), 7.15 (dd, 1H), 4.68 (s, 2H), 3.76 (s, 2H), 2.92 (s, 6H)

Example 218.5-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-ethyl-pyridin-2-onetrifluoroacetate

33 mg of the title compound (yield: 74.1%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 36 mg of1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.88 (s, 1H), 8.55 (d, 1H), 8.26 (dd, 1H), 8.13 (d, 1H), 7.97 (t, 1H),7.72 (d, 1H), 6.62 (d, 1H), 4.68 (s, 2H), 4.15 (q, 2H), 3.77 (s, 2H),1.41 (t, 3H)

Example 219.7-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1,4-dihydro-3,1-benzoxazin-2-onetrifluoroacetate

20 mg of the title compound (yield: 36.6%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(6-bromo-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 31 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 40 mg of7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4,4a,8a-tetrahydro-2H-benzo[d][1,3]oxazin-2-onewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(DMSO-d₆, 400 MHz) δ 10.22 (s, 1H), 8.81 (s, 1H), 8.13 (s, 2H), 7.89 (t,1H), 7.84 (d, 1H), 7.71 (s, 1H), 7.34 (d, 1H), 5.36 (s, 2H), 4.62 (s,2H), 3.56 (s, 2H)

Example 220.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(6-piperazin-1-yl-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

38 mg of the title compound (yield: 70.6%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 55 mg of tert-butyl4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.64 (s, 1H), 8.55 (S, 1H), 8.14 (d, 2H), 8.01 (s, 1H), 7.06(s, 1H), 4.68 (s, 2H), 3.91 (s, 4H), 3.76 (s, 2H), 3.35 (s, 4H), 2.40(s, 3H)

Example 221.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-4H-1,4-benzoxazin-3-onetrifluoroacetate

33 mg of the title compound (yield: 35.5%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 60 mg of6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-Benzo[b][1,4]oxazin-3(4H)-one was used instead of 4-(methanesulfonyl)phenylboronic acid.¹H-NMR (MeOD, 400 MHz) δ 8.57 (s, 1H), 8.17 (s, 1H), 8.06 (s, 1H), 7.30(d, 1H), 7.19 (s, 1H), 7.08 (d, 1H), 4.69 (s, 2H), 4.64 (s, 2H), 3.77(s, 2H), 2.41 (s, 3H)

Example 222.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

377 mg of the title compound (yield: 40.0%) was prepared in the samefashion as Example 17, except that in Step 1, 1000 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 788 mg ofN-(2-methoxyethyl)-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-aminewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.66 (d, 3H), 8.16 (d, 2H), 4.68 (s, 2H), 3.75 (s, 2H), 3.62(dd, 4H), 3.40 (s, 3H), 2.41 (s, 3H)

Example 223.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

38 mg of the title compound (yield: 41.0%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 60 mg of4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazinewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.56 (s, 1H), 8.14 (s, 1H), 8.03 (s, 1H), 7.19 (d, 1H), 7.07(s, 1H), 6.81 (d, 1H), 4.68 (s, 2H), 4.30 (t, 2H), 3.76 (s, 2H), 3.32(t, 2H) 2.95 (s, 3H), 2.37 (s, 3H)

Example 224.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3,4,5-trimethoxyphenyl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

487 mg of the title compound (yield: 50.0%) was prepared in the samefashion as Example 17, except that in Step 1, 1000 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 599 mg of3,4,5-trimethoxyphenylboronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.68 (s,1H), 8.18 (d, 2H), 6.99 (s, 2H), 4.69 (s, 2H), 3.94 (s, 6H), 3.83 (s,3H), 3.76 (s, 2H), 2.43 (s, 3H)

Example 225.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(6-methoxy-3-pyridyl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

46 mg of the title compound (yield: 54.4%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 33 mg of6-methoxy-3-pyridinylboronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.64 (s,1H), 8.48 (s, 1H), 8.17 (d, 1H), 8.14 (d, 1H), 8.03 (s, 1H), 6.95 (s,1H), 4.68 (s, 2H), 3.97 (s, 3H), 3.76 (s, 2H), 2.41 (s, 3H)

Example 226.4-[5-(2-amino-1,3-benzothiazol-5-yl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-onetrifluoroacetate

23 mg of the title compound (yield: 24.9%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 75 mg ofN-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl]acetamidewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.68 (s, 1H), 8.18 (s, 2H), 7.75-7.68 (m, 2H), 7.42 (s, 1H),4.68 (s, 2H), 3.74 (s, 2H), 2.43 (s, 3H)

Example 227.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(2,1,3-benzoxadiazol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

40 mg of the title compound (yield: 46.1%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 53 mg ofbenzo[c][1,2,5]oxadiazol-5-boronic acid pinacol ester was used insteadof 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.81(s, 1H), 8.29 (d, 2H), 8.21 (s, 1H), 8.07 (s, 1H), 7.92 (s, 1H), 4.69(s, 2H), 3.78 (s, 2H), 2.47 (s, 3H)

Example 228.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

33 mg of the title compound (yield: 38.2%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 53 mg of 7-azaindol-5-boronic acidpinacol ester was used instead of 4-(methanesulfonyl)phenylboronic acid.¹H-NMR (MeOD, 400 MHz) δ 8.70 (s, 1H), 8.51 (s, 1H), 8.32 (s, 1H), 8.19(s, 2H), 7.48 (s, 1H), 6.60 (d, 1H), 4.69 (s, 2H), 3.77 (s, 2H), 2.43(s, 3H)

Example 229.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzoxazol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 48.0%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of benzo[d]oxazol-5-ylboronic acid pinacol ester was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.61 (s,1H), 8.50 (s, 1H), 8.38 (s, 1H), 8.18 (s, 1H), 8.10 (s, 1H), 7.36 (s,1H), 7.01 (s, 1H), 4.68 (s, 2H), 3.75 (s, 2H), 2.40 (s, 3H)

Example 230.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

395 mg of the title compound (yield: 40.6%) was prepared in the samefashion as Example 17, except that in Step 1, 1000 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 811 mg of1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrrolidin-2-onewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.69 (s, 1H), 8.19 (s, 2H), 7.82 (d, 2H), 7.77 (d, 2H), 4.69(s, 2H), 4.00 (t, 2H), 3.76 (s, 2H), 2.65 (t, 2H), 2.43 (s, 3H), 2.23(p, 2H)

Example 231.4-[5-(5-acetyl-2-thienyl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 56.6%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 40 mg of5-acetyl-2-thiopheneboronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.75 (s,1H), 8.23-8.17 (m, 2H), 7.90 (s, 1H), 7.67 (s, 1H), 4.67 (s, 2H), 3.75(s, 2H), 2.60 (s, 3H), 2.42 (s, 3H)

Example 232.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-pyrazol-3-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

50 mg of the title compound (yield: 54.4%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 41 mg of[3-(1H-pyrazol-3-yl)phenyl]boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. MS (ESI) m/z=424.2 (M+H)+

Example 233.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1H-indazol-6-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 40.6%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 76 mg of 1H-indazole-6-boronic acidwas used instead of 4-(methanesulfonyl)phenylboronic acid. MS (ESI)m/z=398.2 (M+H)+

Example 234.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one trifluoroacetate

34 mg of the title compound (yield: 51.3%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 30 mg of3-(methanesulfonyl)phenylboronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.74 (s,1H), 8.28-8.19 (m, 3H), 8.07 (s, 2H), 7.80 (s, 1H), 4.69 (s, 2H), 3.77(s, 2H), 3.21 (s, 3H), 2.45 (s, 3H)

Example 235.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

40 mg of the title compound (yield: 59.9%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 59 mg of tert-butyl4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.66 (s, 1H), 8.17 (s, 2H), 7.45 (s, 1H), 7.33 (s, 1H), 7.27(s, 1H), 7.13 (s, 1H), 4.68 (s, 2H), 3.74 (s, 2H), 3.51-3.31 (m, 8H),2.42 (s, 3H)

Example 236.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[4-(morpholine-4-carbonyl)phenyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

33 mg of the title compound (yield: 46.0%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 36 mg of[4-(morpholine-4-carbonyl)phenyl]boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.72 (s,1H), 8.20 (d, 2H), 7.84 (s, 2H), 7.60 (d, 2H), 4.68 (s, 2H), 3.76-3.31(m, 10H), 2.44 (s, 3H)

Example 237.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-morpholinophenyl)-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

50 mg of the title compound (yield: 52.1%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 63 mg of 4-morpholinophenylboronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.62 (s, 1H), 8.16 (s, 1H), 8.10 (s, 1H),7.64 (d, 2H), 7.10 (d, 2H), 4.68 (s, 2H), 3.86 (m, 4H), 3.76 (s, 2H),3.23 (m, 4H), 2.40 (s, 3H)

Example 238.4-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-N,N-dimethyl-benzenesulfonamidetrifluoroacetate

55 mg of the title compound (yield: 54.4%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 68 mg ofN,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamidewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.74 (s, 1H), 8.25 (s, 1H), 8.20 (s, 1H), 7.95 (d, 4H), 4.68(s, 2H), 3.75 (s, 2H), 2.73 (s, 6H), 2.45 (s, 3H)

Example 239.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

8 mg of the title compound (yield: 12.8%) was prepared in the samefashion as Example 17, except that in Step 1, 52 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 50 mg oftrimethyl-[2-[[3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2,4-triazol-1-yl]methoxy]ethyl]silanewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 9.09 (d, 1H), 8.77 (s, 1H), 8.48-8.44 (m, 2H), 8.41 (s, 1H),8.26 (s, 1H), 8.22 (s, 1H), 7.83 (d, 1H), 6.24 (s, 1H), 4.91 (s, 2H),3.74 (s, 2H), 2.46 (s, 3H)

Example 240.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate Step 1: tert-butylN-[3,3-difluoro-2-[[4-[3-methyl-5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamate

50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34, 29 mg of4-ethynyl-1-methyl-1H-pyrazole, 6 mg oftetrakis(triphenylphosphine)palladium (Pd(PPh₃)₄), and 2 mg of copper(I)iodide (CuI) were dissolved in 1.0 mL of N,N-dimethylformamide. To theresulting solution, 45 uL of triethylamine was added and then thesolution was stirred overnight at 90° C. The resulting reaction mixturewas filtered through a celite pad and concentrated under reducedpressure to give a residue. The residue thus obtained was dissolved inethylacetate, washed with distilled water, dried over anhydrousmagnesium sulfate, and concentrated under reduced pressure to give ayellow liquid residue. The residue was purified with silica gel columnchromatography (developing solvent: n-hexane/ethyl acetate=1/1) to give30 mg of the title compound as a yellow solid (yield: 27.6%). MS (ESI)m/z=386.1 (M+H)+

Step 2:2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one

30 mg of tert-butylN-[3,3-difluoro-2-[[4-[3-methyl-5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-5-oxo-1,2,4-triazol-1-yl]methyl]allyl]carbamateprepared in Step 1 was dissolved in 1.0 mL of dichloromethane, and 150uL of trifluoroacetic acid was added thereto. The solution was stirredat room temperature for 2 hours. The reaction mixture thus obtained wasconcentrated, followed by the addition of dichloromethane.Dichloromethane was added to the concentrated reaction mixture, and itwas concentrated under reduced pressure to obtain a yellow liquidresidue. The residue was purified with silica gel column chromatography(developing solvent: dichloromethane/methanol=10/1) to give 19 mg of thetitle compound as a pale yellow solid (yield: 80.2%). ¹H-NMR (MeOD, 400MHz) δ 8.47 (s, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.92 (s, 1H), 7.69 (s,1H), 4.67 (S, 2H), 3.93 (s, 3H), 3.75 (s, 2H), 2.36 (s, 3H)

Example 241.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

22 mg of the title compound (yield: 45.0%) was prepared in the samefashion as Example 240 except that in Step 1, 40 mg of5-ethynyl-N,N-dimethylpyridin-2-amine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.51 (s, 1H),8.26 (s, 1H), 8.17 (s, 1H), 8.01 (s, 1H), 7.78 (d, 1H), 6.88 (d, 1H),4.67 (s, 2H), 3.75 (s, 2H), 3.32 (s, 3H), 3.20 (s, 6H), 2.37 (s, 3H)

Example 242.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 48.6%) was prepared in the samefashion as Example 240 except that in Step 1, 51 mg of4-(5-ethynylpyridin-2-yl)morpholine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.50 (s, 1H),8.33 (s, 1H), 8.16 (s, 1H), 7.99 (s, 1H), 7.70 (d, 1H), 6.84 (d, 1H),4.67 (s, 2H), 3.79 (t, 4H), 3.75 (s, 2H), 3.59 (t, 4H), 2.37 (s, 3H)

Example 243.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

27 mg of the title compound (yield: 55.0%) was prepared in the samefashion as Example 240 except that in Step 1, 70 mg of tert-butyl6-ethynyl-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.46 (s, 1H),8.15 (s, 1H), 7.95 (s, 1H), 6.79 (d, 2H), 6.69 (d, 1H), 4.67 (s, 2H),4.22 (t, 2H), 3.75 (s, 2H), 3.36 (t, 2H), 2.35 (s, 3H)

Example 244.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

22 mg of the title compound (yield: 45.9%) was prepared in the samefashion as Example 240 except that in Step 1, 44 mg of7-ethynyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.51 (s, 1H),8.17 (s, 1H), 8.01 (s, 1H), 7.62 (s, 1H), 7.10 (s, 1H), 4.67 (s, 2H),4.41 (t, 2H), 3.75 (s, 2H), 3.40 (t, 2H), 2.37 (s, 3H)

Example 245.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

24 mg of the title compound (yield: 47.7%) was prepared in the samefashion as Example 240 except that in Step 1, 44 mg of7-ethynyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.49 (s, 1H),8.16 (s, 1H), 7.98 (s, 1H), 7.80 (s, 1H), 7.14 (s, 1H), 4.67 (s, 2H),4.20 (t, 2H), 3.75 (s, 2H), 3.57 (t, 2H), 2.36 (s, 3H)

Example 246.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-oneditrifluoroacetate

24 mg of the title compound (yield: 49.5%) was prepared in the samefashion as Example 240 except that in Step 1, 44 mg of6-ethynyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.51 (s, 1H),8.16 (s, 1H), 8.01 (s, 1H), 7.11 (d, 1H), 6.94 (d, 1H), 4.67 (s, 2H),4.38 (t, 2H), 3.75 (s, 2H), 3.43 (t, 2H), 2.36 (s, 3H)

Example 247.7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-1H-pyrido[2,3-b][1,4]oxazin-2-onetrifluoroacetate

22 mg of the title compound (yield: 44.0%) was prepared in the samefashion as Example 240 except that in Step 1, 47 mg of7-ethynyl-1H,2H,3H-pyrido[2,3-b][1,4]oxazin-2-one was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.54 (s, 1H),8.18 (s, 1H), 8.03 (t, 2H), 7.40 (d, 1H), 4.89 (s, 2H), 4.68 (s, 2H),3.76 (s, 2H), 2.38 (s, 3H)

Example 248.7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-4H-pyrido[3,2-b][1,4]oxazin-3-onetrifluoroacetate

16 mg of the title compound (yield: 32.1%) was prepared in the samefashion as Example 240 except that in Step 1, 47 mg of7-ethynyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.55 (s, 1H),8.17 (s, 1H), 8.14 (s, 1H), 8.05 (s, 1H), 7.49 (s, 1H), 4.71 (s, 2H),4.66 (s, 2H), 3.65 (s, 2H), 2.38 (s, 3H)

Example 249.6-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

25 mg of the title compound (yield: 47.7%) was prepared in the samefashion as Example 240 except that in Step 1, 46 mg of6-ethynyl-1,2,3,4-tetrahydroquinolin-2-one was used instead of4-ethynyl-1-methyl-1H-pyrazole. ¹H-NMR (MeOD, 400 MHz) δ 8.52 (s, 1H),8.18 (s, 1H), 8.02 (s, 1H), 7.43 (s, 1H), 7.40 (d, 1H), 6.90 (d, 1H),4.67 (s, 2H), 3.75 (s, 2H), 3.00 (t, 2H), 2.61 (t, 2H), 2.38 (s, 3H)

Example 250.6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-3-methyl-1,4-dihydroquinazolin-2-onetrifluoroacetate

20 mg of the title compound (yield: 33.6%) was prepared in the samefashion as Example 17, except that in Step 1, 58 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 40 mg of3-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydroquinazolin-2-onewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.60 (s, 1H), 8.17 (s, 1H), 8.08 (s, 1H), 7.51 (d, 1H), 7.47(s, 1H), 6.88 (d, 1H), 4.69 (s, 2H), 4.56 (s, 2H), 3.76 (s, 2H), 3.01(s, 3H), 2.40 (s, 3H)

Example 251.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[1-(difluoromethyl)pyrazol-4-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

22 mg of the title compound (yield: 51.4%) was prepared in the samefashion as Example 17, except that in Step 1, 49 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 26 mg of1-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.70 (d, 2H), 8.21 (m, 3H), 7.57 (t, 1H), 4.69 (s, 2H), 3.61(s, 2H), 2.40 (s, 3H)

Example 252.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-isopropylpyrazol-4-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 75.4%) was prepared in the samefashion as Example 17, except that in Step 1, 51 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 17 mg of(1-isopropylpyrazole-4-yl)boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.64 (s,1H), 8.10 (m, 4H), 4.64 (m, 3H), 3.76 (s, 2H), 2.37 (s, 3H), 1.56 (d,6H)

Example 253.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-onetrifluoroacetate

37 mg of the title compound (yield: 98.8%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.08 (m, 3H),7.65 (d, 2H), 7.46 (m, 3H), 4.69 (s, 2H), 3.77 (s, 2H), 3.20 (s, 2H),2.11 (s, 3H)

Example 254.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-oneditrifluoroacetate

28 mg of the title compound (yield: 73.6%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 34 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.06 (d, 2H), 7.39 (m, 2H), 7.32 (m, 3H), 7.13 (d, 2H), 4.69(s, 2H), 3.76 (s, 2H), 3.49 (t, 4H), 3.41 (t, 4H), 2.11 (s, 3H)

Example 255.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-onetrifluoroacetate

32 mg of the title compound (yield: 86.2%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 24 mg of2-(trifluoromethyl)pyridin-5-boronic acid pinacol ester was used insteadof 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.75(s, 1H), 8.09 (t, 2H), 7.96 (d, 1H), 7.51 (m, 3H), 4.69 (s, 2H), 3.77(s, 2H), 2.13 (s, 3H)

Example 256.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]-2-methyl-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 100%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of6-(dimethylamino)pyridin-3-boronic acid pinacol ester was used insteadof 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.07(s, 1H), 7.96 (m, 2H), 7.46 (m, 3H), 7.25 (d, 1H), 4.69 (s, 2H), 3.77(s, 2H), 3.33 (s, 6H), 2.16 (s, 3H)

Example 257.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)-2-methyl-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 82.8%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 8.06 (s, 1H), 7.39 (t, 2H), 7.32 (m, 1H), 6.91 (d, 1H), 6.80 (m,2H), 6.01 (s, 2H), 4.68 (d, 2H), 3.76 (d, 2H), 2.06 (d, 3H)

Example 258.6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

31 mg of the title compound (yield: 81.6%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.06 (s, 1H), 7.86 (m, 3H), 7.04 (s, 2H), 4.69 (s, 2H), 3.77(s, 2H), 2.99 (t, 2H), 2.61 (t, 2H), 2.31 (s, 3H), 2.11 (s, 3H)

Example 259.6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

29 mg of the title compound (yield: 77.0%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 8.07 (s, 1H), 7.41 (t, 2H), 7.35 (m, 1H), 7.27 (m,1H), 7.23 (d, 2H), 4.69 (s, 2H), 3.77 (s, 2H), 3.41 (s, 3H), 2.99 (t,2H), 2.68 (t, 2H), 2.12 (s, 3H)

Example 260.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)-2-methyl-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

24 mg of the title compound (yield: 73.6%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 19 mg of 1-ethylpyrazol-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.05 (s, 1H), 7.88 (s, 1H), 7.67 (s, 1H),7.52 (d, 1H), 7.38 (t, 1H), 7.27 (d, 1H), 4.69 (s, 2H), 4.26 (q, 2H),3.77 (s, 2H), 2.24 (s, 3H), 1.52 (t, 3H)

Example 261.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[1-(difluoromethyl)pyrazol-4-yl]-2-methyl-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

22 mg of the title compound (yield: 52.3%) was prepared in the samefashion as Example 17, except that in Step 1, 49 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 26 mg of1-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.27 (s, 1H), 8.06 (s, 1H), 7.92 (s, 1H), 7.70 (d, 2H), 7.39(m, 2H), 4.69 (s, 2H), 3.77 (s, 2H), 2.24 (s, 3H)

Example 262.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-isopropylpyrazol-4-yl)-2-methyl-phenyl]-1,2,4-triazol-3-onetrifluoroacetate

40 mg of the title compound (yield: 92.7%) was prepared in the samefashion as Example 17, except that in Step 1, 51 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 17 mg of(1-isopropylpyrazole-4-yl)boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.97 (d,2H), 7.67 (s, 1H), 7.40 (m, 3H), 4.62 (m, 3H), 3.77 (s, 2H), 2.24 (s,3H), 1.56 (d, 6H)

Example 263.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[3-(1H-1,2,4-triazol-3-yl)phenyl]phenyl]-1,2,4-triazol-3-onetrifluoroacetate

8 mg of the title compound (yield: 13.6%) was prepared in the samefashion as Example 17, except that in Step 1, 57 mg of tert-butylN-[2-[[4-(3-bromo-2-methyl-phenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 53 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 50 mg oftrimethyl-[2-[[3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2,4-triazole-1-yl]methoxy]ethyl]silanewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.67 (s, 1H), 8.65-8.63 (m, 1H), 8.12-8.10 (m, 2H), 8.08-8.06(m, 2H), 7.59 (t, 1H), 7.48 (d, 1H), 7.47-7.38 (m, 2H), 5.60 (bs, 1H),4.69 (s, 2H), 3.73 (s, 2H), 2.15 (s, 3H)

Example 264.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

23 mg of the title compound (yield: 28.0%) was prepared in the samefashion as Example 17, except that in Step 1, 100 mg of tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 54 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 48 mg of 1-ethylpyrazol-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.02 (s, 1H), 7.94 (s, 1H), 7.83 (s, 1H),7.57 (d, 2H), 7.35 (d, 2H), 4.86 (s, 2H), 4.60 (s, 2H), 4.21 (q, 2H),3.68 (s, 2H), 1.49 (t, 3H)

Example 265.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

7 mg of the title compound (yield: 10.5%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 54 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.04 (d, 2H),7.99 (s, 1H), 7.89 (d, 2H), 7.74 (d, 2H), 7.50 (d, 2H), 4.96 (s, 2H),4.61 (s, 2H), 3.69 (s, 2H), 3.17 (s, 3H)

Example 266.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

9 mg of the title compound (yield: 11.8%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 54 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 59 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 7.95 (s, 1H), 7.61 (d, 2H), 7.58 (d, 2H), 7.41 (d, 2H), 7.11(d, 2H), 4.90 (s, 2H), 4.60 (s, 2H), 3.66 (s, 2H), 3.47 (d, 4H), 3.39(d, 4H)

Example 267.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

12 mg of the title compound (yield: 18.4%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 54 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of(6-(dimethylamino)pyridine-3-yl)boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.19 (s,1H), 8.18 (d, 1H), 7.97 (s, 1H), 7.64 (d, 2H), 7.47 (d, 2H), 7.19 (d,1H), 4.93 (s, 2H), 4.60 (s, 2H), 3.69 (s, 2H), 3.29 (s, 6H)

Example 268.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

12 mg of the title compound (yield: 19.7%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 54 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of3,4-(methylenedioxy)phenylboronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.95 (s,1H), 7.56 (d, 2H), 7.39 (d, 2H), 7.09 (d, 2H), 6.89 (d, 1H), 5.99 (s,2H), 4.90 (s, 2H), 4.60 (s, 2H), 3.68 (s, 2H)

Example 269.6-[4-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

7 mg of the title compound (yield: 9.9%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 54 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 44 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 7.96 (s, 1H), 7.61 (d, 2H), 7.40 (d, 2H), 7.32 (s, 2H), 4.90(s, 2H), 4.60 (s, 2H), 3.69 (s, 2H), 3.01 (t, 2H), 2.60 (t, 2H), 2.33(s, 3H)

Example 270.5-[4-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-onetrifluoroacetate

8 mg of the title compound (yield: 12.5%) was prepared in the samefashion as Example 17, except that in Step 1, 70 mg of tert-butylN-[2-[[4-[(4-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 54 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 38 mg of1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.01 (d, 1H), 7.96 (s, 1H), 7.87 (dd, 1H), 7.58 (d, 2H), 7.43 (d, 2H),6.65 (d, 1H), 4.90 (s, 2H), 4.60 (s, 2H), 4.13 (q, 2H), 3.69 (s, 2H),1.39 (t, 3H)

Example 271.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

25 mg of the title compound (yield: 75.9%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 55 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 19 mg of 1-ethylpyrazol-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 8.04 (s, 1H), 7.97 (s, 1H), 7.84 (s, 1H),7.55 (t, 2H), 7.38 (t, 1H), 7.20 (d, 1H), 4.89 (s, 2H), 4.60 (s, 2H),4.23 (dd, 2H), 3.68 (s, 2H), 1.50 (t, 3H)

Example 272.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

33 mg of the title compound (yield: 87.4%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 55 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.03 (t, 3H),7.90 (d, 2H), 7.71 (m, 2H), 7.54 (t, 1H), 7.44 (d, 1H), 4.98 (s, 2H),4.60 (s, 2H), 3.69 (s, 2H), 3.17 (s, 3H)

Example 273.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

34 mg of the title compound (yield: 98.8%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 55 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of(6-(dimethylamino)pyridine-3-yl)boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.25(dd, 1H), 8.19 (d, 1H), 8.00 (s, 1H), 7.66 (s, 1H), 7.62 (d, 1H), 7.52(t, 1H), 7.40 (d, 1H), 7.27 (d, 1H), 4.96 (s, 2H), 4.60 (s, 2H), 3.69(s, 2H), 3.33 (s, 6H)

Example 274.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

33 mg of the title compound (yield: 94.2%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 55 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of3,4-(methylenedioxy)phenylboronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.98 (s,2H), 7.53 (d, 2H), 7.42 (t, 1H), 7.29 (d, 1H), 7.09 (t, 2H), 6.90 (d,1H), 5.99 (s, 2H), 4.92 (s, 2H), 4.60 (s, 2H), 3.68 (s, 2H)

Example 275.6-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

26 mg of the title compound (yield: 66.7%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 55 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 7.99 (s, 1H), 7.58 (m, 2H), 7.43 (t, 1H), 7.30 (m, 3H), 4.93(s, 2H), 4.60 (s, 2H), 3.68 (s, 2H), 3.01 (t, 2H), 2.59 (t, 2H), 2.33(s, 3H)

Example 276.6-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

28 mg of the title compound (yield: 73.6%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 55 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 7.99 (s, 1H), 7.62 (m, 2H), 7.56 (t, 1H), 7.51 (s,1H), 7.46 (t, 1H), 7.32 (d, 1H), 7.21 (d, 1H), 4.94 (s, 2H), 4.60 (s,2H), 3.68 (s, 2H), 3.40 (s, 3H), 3.00 (t, 2H), 2.67 (t, 2H)

Example 277.5-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-onetrifluoroacetate

30 mg of the title compound (yield: 86.2%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(3-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 55 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 8.02 (d, 2H), 7.88 (m, 1H), 7.56 (m, 2H), 7.46 (t, 1H), 7.33 (d, 1H),6.65 (d, 1H), 4.93 (s, 2H), 4.60 (s, 2H), 4.14 (q, 2H), 3.69 (s, 2H),1.40 (t, 3H)

Example 278.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

26 mg of the title compound (yield: 78.2%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 19 mg of 1-ethylpyrazol-4-boronicacid pinacol ester was used instead of 4-(methanesulfonyl)phenylboronicacid. ¹H-NMR (MeOD, 400 MHz) δ 7.81 (s, 1H), 7.55 (d, 2H), 7.35 (m, 3H),7.27 (d, 1H), 4.98 (s, 2H), 4.55 (s, 2H), 4.26 (q, 2H), 3.66 (s, 2H),1.52 (t, 3H)

Example 279.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

30 mg of the title compound (yield: 78.2%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25. ¹H-NMR (MeOD, 400 MHz) δ 8.03 (d, 2H),7.60 (d, 2H), 7.49 (m, 3H), 7.41 (m, 1H), 7.32 (m, 1H), 4.87 (s, 2H),4.46 (s, 2H), 3.61 (s, 2H), 3.20 (s, 3H)

Example 280.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

27 mg of the title compound (yield: 69.0%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 34 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 7.47 (m, 3H), 7.28 (m, 4H), 7.12 (d, 2H), 4.88 (s, 2H), 4.51(s, 2H), 3.64 (s, 2H), 3.50 (t, 4H), 3.41 (t, 4H), 3.33 (m, 2H)

Example 281.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 100%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of(6-(dimethylamino)pyridine-3-yl)boronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.94 (m,2H), 7.75 (s, 1H), 7.48 (m, 2H), 7.39 (m, 1H), 7.33 (m, 1H), 7.24 (d,1H), 4.88 (s, 2H), 4.52 (s, 2H), 3.67 (d, 2H), 3.32 (s, 6H)

Example 282.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

35 mg of the title compound (yield: 100%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of3,4-(methylenedioxy)phenylboronic acid was used instead of4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 7.39 (m,3H), 7.32 (t, 1H), 7.23 (m, 1H), 6.89 (d, 1H), 6.75 (m, 2H), 6.01 (s,2H), 4.86 (s, 2H), 4.50 (s, 2H), 3.64 (s, 2H)

Example 283.6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-onetrifluoroacetate

25 mg of the title compound (yield: 65.5%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 7.39 (m, 3H), 7.31 (t, 1H), 7.27 (m, 1H), 6.99 (d, 2H), 4.87(s, 2H), 4.94 (s, 2H), 3.64 (s, 2H), 2.99 (t, 2H), 2.61 (t, 2H), 2.31(s, 3H)

Example 284.6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

28 mg of the title compound (yield: 72.4%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 25 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-yl)boronic acid pinacolester was used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR(MeOD, 400 MHz) δ 7.40 (d, 3H), 7.34 (d, 1H), 7.30 (t, 1H), 7.21 (t,3H), 4.88 (s, 2H), 4.49 (s, 2H), 3.64 (s, 2H), 3.41 (s, 3H), 2.97 (t,2H), 2.68 (t, 2H)

Example 285.5-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-onetrifluoroacetate

17 mg of the title compound (yield: 49.4%) was prepared in the samefashion as Example 17, except that in Step 1, 40 mg of tert-butylN-[2-[[4-[(2-bromophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 56 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 22 mg of1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was usedinstead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD, 400 MHz)δ 7.76 (d, 1H), 7.62 (s, 1H), 7.46 (m, 3H), 7.38 (t, 1H), 7.32 (m, 1H),6.58 (d, 1H), 4.90 (s, 2H), 4.49 (s, 2H), 4.10 (q, 2H), 3.64 (s, 2H),1.40 (t, 3H)

Example 286.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

37 mg of the title compound (yield: 75.7%) was prepared in the samefashion as Example 100, except that in Step 1, 48 mg of1-ethyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrazolewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.01 (d, 2H), 7.85 (s, 1H), 7.58 (s, 4H), 7.27 (d, 1H), 7.13 (d, 1H),5.06 (s, 2H), 4.60 (s, 2H), 4.22 (dd, 2H), 3.68 (s, 2H), 1.50 (t, 3H)

Example 287.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 58.9%) was prepared in the samefashion as Example 100, except that in Step 1, 48 mg of1-ethyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrazolewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.07 (s, 1H), 8.00 (s, 1H), 7.88 (s, 1H), 7.77 (s, 1H), 7.50 (d, 1H),7.43 (d, 1H), 7.37 (m, 2H), 7.15 (d, 1H), 5.08 (s, 2H), 4.60 (s, 2H),4.24 (q, 2H), 3.68 (s, 2H), 1.51 (t, 3H)

Example 288.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

27 mg of the title compound (yield: 51.8%) was prepared in the samefashion as Example 100, except that in Step 1, 52 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 50 mg of1-ethyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrazolewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.01 (d, 2H), 7.85 (s, 1H), 7.59 (m, 6H), 5.10 (s, 2H), 4.60 (s, 2H),4.22 (q, 2H), 3.68 (s, 2H), 1.50 (t, 3H)

Example 289.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

29 mg of the title compound (yield: 57.1%) was prepared in the samefashion as Example 100, except that in Step 1, 52 mg of tert-butylN-[2-[[4-(4-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 42 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 50 mg of1-ethyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrazolewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.04 (d, 2H), 7.86 (d, 2H), 7.68 (d, 1H), 7.59 (s, 1H), 7.49 (d, 2H),7.38 (t, 1H), 5.11 (s, 2H), 4.60 (s, 2H), 4.24 (dd, 2H), 3.68 (s, 2H),1.51 (t, 3H)

Example 290.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[4-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

15 mg of the title compound (yield: 30.3%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 48 mg of1-ethyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrazolewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.70 (s, 1H), 8.19 (s, 2H), 8.11 (s, 1H), 7.91 (s, 1H), 7.73(s, 4H), 4.70 (s, 2H), 4.25 (q, 2H), 3.77 (s, 2H), 2.43 (s, 3H), 1.50(t, 3H)

Example 291.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[3-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-onetrifluoroacetate

27 mg of the title compound (yield: 56.0%) was prepared in the samefashion as Example 17, except that in Step 1, 50 mg of tert-butylN-[2-[[4-(5-bromo-3-methyl-2-pyridyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 34 was used instead of tert-butylN-[2-[[4-(3-bromophenyl)-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 25 and 48 mg of1-ethyl-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrazolewas used instead of 4-(methanesulfonyl)phenylboronic acid. ¹H-NMR (MeOD,400 MHz) δ 8.71 (s, 1H), 8.20 (s, 1H), 8.14 (s, 1H), 7.95 (s, 1H), 7.90(s, 1H), 7.66 (d, 1H), 7.54 (m, 2H), 4.70 (s, 2H), 4.25 (q, 2H), 3.78(s, 2H), 2.44 (s, 3H), 1.52 (t, 3H)

Example 292.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-pyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

22 mg of the title compound (yield: 57.0%) was prepared in the samefashion as Example 100, except that in Step 1, 25 mg of1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]ethanonewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.97 (s, 1H), 7.83 (s, 2H), 7.55 (m, 2H), 5.03 (s, 2H), 4.59 (s, 2H),3.68 (s, 2H)

Example 293.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

13 mg of the title compound (yield: 28.0%) was prepared in the samefashion as Example 100, except that in Step 1, 20 mg of(1-methylsulfonylpyrazol-4-yl)boronic acid was used instead of4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.42 (s, 1H), 8.12(s, 1H), 7.98 (s, 1H), 7.22 (d, 1H), 7.13 (d, 1H), 5.06 (s, 2H), 4.59(s, 2H), 3.68 (s, 2H), 3.45 (s, 3H)

Example 294.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-cyclopropylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

38 mg of the title compound (yield: 77.6%) was prepared in the samefashion as Example 100, except that in Step 1, 32 mg of1-cyclopropylsulfonyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ8.40 (s, 1H), 8.10 (s, 1H), 7.98 (s, 1H), 7.21 (d, 1H), 7.12 (d, 1H),5.06 (s, 2H), 4.59 (s, 2H), 3.69 (s, 2H), 2.97 (m, 1H), 1.41 (m, 2H),1.23 (m, 2H)

Example 295.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(cyclopropylmethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

31 mg of the title compound (yield: 72.0%) was prepared in the samefashion as Example 100, except that in Step 1, 27 mg of1-(cyclopropylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.95 (d, 2H), 7.67 (s, 1H), 7.05 (dd, 2H), 5.03 (s, 2H), 4.59 (s, 2H),4.00 (d, 2H), 3.68 (s, 2H), 1.30 (m, 1H), 0.63 (m, 2H), 0.42 (m, 2H)

Example 296.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

12 mg of the title compound (yield: 29.0%) was prepared in the samefashion as Example 100, except that in Step 1, 22 mg of1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole wasused instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.96 (s, 2H), 7.85 (s, 1H), 7.66 (s, 1H), 7.06 (d, 1H), 7.01 (d, 1H),5.03 (s, 2H), 4.59 (s, 2H), 3.90 (s, 3H), 3.67 (s, 2H)

Example 297.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-benzylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

23 mg of the title compound (yield: 48.6%) was prepared in the samefashion as Example 100, except that in Step 1, 30 mg of1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole wasused instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.94 (d, 2H), 7.71 (s, 1H), 7.34 (m, 3H), 7.27 (m, 2H), 7.04 (dd, 2H),5.34 (s, 2H), 5.02 (s, 2H), 4.58 (s, 2H), 3.67 (s, 2H)

Example 298.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-oneditrifluoroacetate

17 mg of the title compound (yield: 35.9%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 59 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 40 mg of tert-butyl4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine-1-carboxylatewas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.97 (s, 1H), 7.54 (d, 2H), 7.07 (t, 3H), 5.01 (s, 2H), 4.59 (s, 2H),3.67 (s, 2H), 3.49 (t, 4H), 3.39 (m, 4H)

Example 299.5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-ethyl-pyridin-2-onetrifluoroacetate

28 mg of the title compound (yield: 65.0%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 59 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 26 mg of1-ethyl-6-oxo-1,6-dihydropyridine-3-boronic acid pinacol ester was usedinstead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.05 (d,2H), 7.75 (q, 1H), 7.11 (s, 1H), 5.02 (s, 2H), 4.59 (s, 2H), 4.08 (q,2H), 3.69 (s, 2H), 1.37 (t, 3H)

Example 300.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

26 mg of the title compound (yield: 59.2%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 59 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 26 mg of2-(1,3-benzodioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasused instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.97 (s, 1H), 7.08 (m, 3H), 6.85 (d, 1H), 6.01 (s, 2H), 5.00 (s, 2H),4.59 (s, 2H), 3.68 (s, 2H)

Example 301.6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-onetrifluoroacetate

25 mg of the title compound (yield: 52.4%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 59 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 30 mg of(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)boronic acid pinacolester was used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400MHz) δ 7.98 (s, 1H), 7.49 (m, 2H), 7.16 (t, 2H), 5.02 (s, 2H), 4.59 (s,2H), 3.68 (s, 2H), 3.36 (s, 3H), 2.96 (t, 2H), 2.64 (t, 2H)

Example 302.2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-onetrifluoroacetate

21 mg of the title compound (yield: 51.4%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 59 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 23 mg of1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole wasused instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.96 (s, 2H), 7.70 (s, 1H), 6.95 (s, 1H), 4.98 (s, 2H), 4.58 (s, 2H),4.20 (q, 2H), 3.67 (s, 2H), 1.47 (t, 3H),

Example 303.2-(2-(aminomethyl)-3,3-difluoroallyl)-4-((5-(6-(dimethylamino)pyridin-3-yl)-3-fluorothiophen-2-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-onetrifluoroacetate

2 mg of the title compound (yield: 3.9%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 59 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 26 mg of6-(dimethylamino)pyridine-3-boronic acid pinacol ester was used insteadof 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ 8.29 (d, 1H),7.95 (s, 1H), 7.74 (m, 1H), 7.05 (s, 1H), 6.71 (d, 1H), 5.00 (s, 2H),4.57 (s, 2H), 3.47 (s, 2H), 3.13 (s, 6H)

Example 304.6-(5-((1-(2-(aminomethyl)-3,3-difluoroallyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)methyl)-4-fluorothiophen-2-yl)-8-methyl-3,4-dihydroquinolin-2(1H)-onetrifluoroacetate

2 mg of the title compound (yield: 4.8%) was prepared in the samefashion as Example 100, except that in Step 1, 50 mg of tert-butylN-[2-[[4-[(5-bromo-3-fluoro-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 59 was used instead of tert-butylN-[2-[[4-(5-bromo-2-thienyl)methyl]-5-oxo-1,2,4-triazol-1-yl]methyl]-3,3-difluoro-allyl]carbamateprepared in Reference Example 41 and 30 mg of8-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-boronic acid pinacol esterwas used instead of 4-acetylphenylboronic acid. ¹H-NMR (MeOD, 400 MHz) δ7.96 (s, 1H), 7.31 (s, 2H), 7.15 (s, 1H), 5.01 (s, 2H), 4.58 (s, 2H),3.65 (s, 2H), 2.99 (t, 2H), 2.59 (t, 2H), 2.30 (s, 3H)

Compounds from the Examples are shown in Table 1.

TABLE 1* Ex No Structure Chemical Name    1

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazol-3-one  2

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3-bromophenyl)-1,2,4-triazol-3-one  3

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3,4-difluorophenyl)-1,2,4-triazol-3-one  4

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-3-fluoro-phenyl)-1,2,4-triazol- 3-one  5

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazol- 3-one  6

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-methyl-phenyl)-1,2,4-triazol 3-one  7

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-pyridyl)-1,2,4-triazol-3-one  8

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-2-pyridyl)-1,2,4-triazol-3-one  9

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-pyridyl)-1,2,4-triazol-3-one  10

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(2-bromo-4-pyridyl)-1,2,4-triazol-3-one  11

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-methyl-2-pyridyl)-1,2,4- triazol-3-one  12

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-4-methyl-3-pyridyl)-1,2,4- triazol-3-one  13

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-5-methyl-3-pyridyl)-1,2,4- triazol-3-one  14

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-fluoro-2-pyridyl)-1,2,4- triazol-3-one  15

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-methyl-2-pyridyl)-1,2,4- triazol-3-one  16

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromopyrazin-2-yl)-1,2,4-triazol-3-one  17

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]- 1,2,4-triazol-3-one  18

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4- triazol-3-one  19

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(trifluoromethyl)-3-pyridyl]phenyl]- 1,2,4-triazol-3-one  20

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]phenyl]- 1,2,4-triazol-3-one  21

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1,2,4- triazol-3-one  22

6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one  23

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)phenyl]-1,2,4- triazol-3-one  24

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [3-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4- triazol-3-one  25

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [3-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one  26

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-[6-(trifluoromethyl)-3- pyridyl]phenyl]-1,2,4-triazol-3-one 27

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-3- fluoro-phenyl]-1,2,4-triazol-3-one 28

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-3-fluoro- phenyl]-1,2,4-triazol-3-one  29

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-fluoro-phenyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one  30

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-3-fluoro-phenyl]- 1,2,4-triazol-3-one  31

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [2-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4- triazol-3-one  32

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [2-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one  33

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-[6-(trifluoromethyl)-3- pyridyl]phenyl]-1,2,4-triazol-3-one 34

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2- fluoro-phenyl]-1,2,4-triazol-3-one 35

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-fluoro- phenyl]-1,2,4-triazol-3-one  36

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-fluoro-phenyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one  37

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-fluoro-phenyl]- 1,2,4-triazol-3-one  38

2-(2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-3-pyridyl]- 1,2,4-triazol-3-one  39

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-3-pyridyl]- 1,2,4-triazol-3-one  40

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-3- pyridyl]-1,2,4-triazol-3-one  41

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-3- pyridyl]-1,2,4-triazol-3-one  42

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-3-pyridyl]- 1,2,4-triazol-3-one  43

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one  44

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one  45

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-3-pyridyl]-1,2,4 triazol-3-one  46

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-2-pyridyl]- 1,2,4-triazol-3-one  47

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-2-pyridyl]- 1,2,4-triazol-3-one  48

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-2- pyridyl]-1,2,4-triazol-3-one  49

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-2- pyridyl]-1,2,4-triazol-3-one  50

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-2-pyridyl]- 1,2,4-triazol-3-one  51

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one  52

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one  53

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4- triazol-3-one  54

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-methylsulfonylphenyl)-2-pyridyl]- 1,2,4-triazol-3-one  55

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-piperazin-1-ylphenyl)-2-pyridyl]- 1,2,4-triazol-3-one  56

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(trifluoromethyl)-3-pyridyl]-2- pyridyl]-1,2,4-triazol-3-one  57

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2- pyridyl]-1,2,4-triazol-3-one  58

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-pyridyl]- 1,2,4-triazol-3-one  59

6-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-4-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one  60

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4- triazol-3-one  61

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-methylsulfonylphenyl)-4-pyridyl]- 1,2,4-triazol-3-one  62

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-piperazin-1-ylphenyl)-4-pyridyl]- 1,2,4-triazol-3-one  63

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[6-(dimethylamino)-3-pyridyl]-4- pyridyl]-1,2,4-triazol-3-one  64

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1,3-benzodioxol-5-yl)-4-pyridyl]- 1,2,4-triazol-3-one  65

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one  66

6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one  67

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1-ethylpyrazol-4-yl)-4-pyridyl]-1,2,4- triazol-3-one  68

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methylsulfonylphenyl)-2- pyridyl]-1,2,4-triazol-3-one  69

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-piperazin-1-ylphenyl)-2- pyridyl]-1,2,4-triazol-3-one  70

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one  71

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]-3 methyl-2-pyridyl]-1,2,4-triazol-3-one 72

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-methyl-2- pyridyl]-1,2,4-triazol-3-one  73

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one  74

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-1-methyl-3,4-dihydroquinolin- 2-one  75

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-methyl-2- pyridyl]-1,2,4-triazol-3-one  76

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-(4-methylsulfonylphenyl)-3- pyridyl]-1,2,4-triazol-3-one  77

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-one  78

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-5-methyl-3-pyridyl]-1,2,4-triazol-3-one  79

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-5-methyl-3- pyridyl]-1,2,4-triazol-3-one  80

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one  81

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-1-methyl-3,4-dihydroquinolin- 2-one  82

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-methylsulfonylphenyl)-2- pyridyl]-1,2,4-triazol-3-one  83

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-piperazin-1-ylphenyl)-2- pyridyl]-1,2,4-triazol-3-one  84

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one  85

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-fluoro-2- pyridyl]-1,2,4-triazol-3-one  86

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-l,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one  87

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-1-methyl-3,4-dihydroquinolin- 2-one  88

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-fluoro-2- pyridyl]-1,2,4-triazol-3-one  89

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-methylsulfonylphenyl)pyrazin-2- yl]-1,2,4-triazol-3-one  90

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-piperazin-1-ylphenyl)pyrazin-2-yl]- 1,2,4-triazol-3-one  91

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(trifluoromethyl)-3-pyridyl]pyrazin- 2-yl]-1,2,4-triazol-3-one  92

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]pyrazin- 2-yl]-1,2,4-triazol-3-one  93

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)pyrazin-2-yl]- 1,2,4-triazol-3-one  94

6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]pyrazin-2-yl]-1-methyl-3,4-dihydro-1H-quinolin-2- one  95

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)pyrazin-2-yl]- 1,2,4-triazol-3-one  96

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-benzyloxyphenyl)methyl]-1,2,4- triazol-3-one  97

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-2-thienyl)methyl]-1,2,4- triazol-3-one  98

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-bromo-2-thienyl)methyl]-1,2,4- triazol-3-one  99

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-3-methyl-2-thienyl)methyl]- 1,2,4-triazol-3-one 100

4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]- 1,2,4-triazol-3-one 101

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)-2- thienyl]methyl]-1,2,4-triazol-3-one 102

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-methylsulfonylphenyl)-2- thienyl]methyl]-1,2,4-triazol-3-one 103

3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2- thienyl]-N,N-dimethyl-benzenesulfonamide 104

4-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2- thienyl]-N-methyl-benzamide105

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3,4,5-trimethoxyphenyl)-2- thienyl]methyl]-1,2,4-triazol-3-one 106

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)-2- thienyl]methyl]-1,2,4-triazol-3-one 107

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-piperazin-1-ylphenyl)-2- thienyl]methyl]-1,2,4-triazol-3-one 108

4-[[5-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one 109

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[4-(morpholine-4-carbonyl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 110

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-pyrazol-3-yl)phenyl]-2- thienyl]methyl]-1,2,4-triazol-3-one111

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 112

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-2- thienyl]methyl]-1,2,4-triazol-3-one113

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(6-methoxy-3-pyridyl)-2-thienyl]methyl]-1,2,4-triazol-3-one 114

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-piperazin-1-yl-3-pyridyl)-2- thienyl]methyl]-1,2,4-triazol-3-one115

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-5-fluoro-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3- one 116

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(2-aminopyrimidin-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 117

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-ethoxypyrimidin-5-yl)-2- thienyl]methyl]-1,2,4-triazol-3-one 118

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-2-thienyl]methyl]-1,2,4-triazol-3- one 119

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 120

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-chloro-3-methyl-imidazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 121

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-pyridin-2-one 122

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-ethyl-pyridin-2-one 123

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-isopropyl-pyridin-2-one 124

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 125

4-[[5-(1-acetyl-3,6-dihydro-2H-pyridin-4- yl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4- triazol-3-one 126

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 127

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-indazol-6-yl)-2-thienyl]methyl]- 1,2,4-triazol-3-one 128

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-([1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 129

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2,1,3-benzoxadiazol-5-yl)-2- thienyl]methyl]-1,2,4-triazol-3-one130

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-7-fluoro-indolin-2-one 131

N-[6-[5-[[1-[2-(aminomethyl)-3,3- difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,3-benzothiazol-2- yl]acetamide 132

7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-2H-isoquinolin-1- one 133

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-1H-quinolin-2-one 134

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one 135

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-1H-quinolin-2-one 136

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-3,4-dihydro-1H- quinolin-2-one 137

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-1H-quinolin-2-one 138

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2- one 139

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-2-thienyl]methyl]-1,2,4- triazol-3-one 140

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-thienyl]methyl]-1,2,4- triazol-3-one 141

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4H-1,4-benzoxazin-3-one 142

7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2- one 143

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2- one 144

7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4-methyl-1,4-benzoxazin-3-one 145

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-2-thienyl]methyl]-1,2,4-triazol-3- one 146

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)-2- thienyl]methyl]-1,2,4-triazol-3-one 147

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)-2- thienyl]methyl]-1,2,4-triazol-3-one 148

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 149

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]-2- thienyl]methyl]-1,2,4-triazol-3-one150

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[4-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 151

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one 152

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-3,4-dihydroquinolin-2- one 153

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[4-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 154

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one 155

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one 156

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3- one 157

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3- one 158

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one 159

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one 160

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2- pyridyl]-1,2,4-triazol-3-one 161

7-[(E)-2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4- yl]methyl]-2-thienyl]vinyl]-1H-pyrido[2,3-b][1,4]oxazin-2-one 162

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-2-thienyl]methyl]-1,2,4- triazol-3-one 163

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 164

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4- triazol-3-one 165

6-[2-[5-[[1-[2-(aminomethyl)-3,3- difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-3,4- dihydro-1H-quinolin-2-one 166

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3- b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 167

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-pyrido[3,2- b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 168

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3- b][1,4]oxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 169

7-[2-[5-[[1-[2-(aminomethyl)-3,3- difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-1H- pyrido[2,3-b][1,4]oxazin-2-one 170

7-[2-[5-[[1-[2-(aminomethyl)-3,3- difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-4H- pyrido[3,2-b][1,4]oxazin-3-one 171

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 172

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(2-thienyl)ethyl]-1,2,4-triazol-3-one 173

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methylsulfonylphenyl)-2- thienyl]ethyl]-1,2,4-triazol-3-one 174

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-piperazin-1-ylphenyl)-2- thienyl]ethyl]-1,2,4-triazol-3-one 175

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-one 176

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-one 177

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1,3-benzodioxol-5-yl)-2- thienyl]ethyl]-1,2,4-triazol-3-one 178

6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one 179

6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2- one 180

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [2-[5-(1-ethylpyrazol-4-yl)-2-thienyl]ethyl]-1,2,4-triazol-3-one 181

3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yllmethyl]-2-thienyl]-N,N-dimethyl-benzamide 182

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3-methyl-1,4-dihydroquinazolin- 2-one 183

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one 184

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-isopropylpyrazol-4-yl)-2- thienyl]methyl]-1,2,4-triazol-3-one 185

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 186

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3-methyl-1,4-dihydroquinazolin- 2-one 187

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-isopropyl-pyridin-2-one 188

4-[[4-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one 189

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-fluoro-1H-quinolin-2-one 190

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-pyridin-2-one 191

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1,4-dihydro-3,1-benzoxazin-2- one 192

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3,4-dihydro-1H-quinolin-2-one 193

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-ethyl-pyridin-2-one 194

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one 195

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-isopropylpyrazol-4-yl)-2- thienyl]methyl]-1,2,4-triazol-3-one 196

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 197

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[6-(4-methylsulfonylphenyl)benzothiophen-2- yl]methyl]-1,2,4-triazol-3-one 198

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[6-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]- 1,2,4-triazol-3-one 199

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[6-[6-(trifluoromethyl)-3-pyridyl]benzothiophen-2-yl]methyl]- 1,2,4-triazol-3-one 200

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[6-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]- 1,2,4-triazol-3-one 201

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one 202

6-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-8-methyl- 3,4-dihydro-1H-quinolin-2-one203

6-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-1-methyl- 3,4-dihydroquinolin-2-one 204

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1-ethylpyrazol-4-yl)benzothiophen-2- yl]methyl]-1,2,4-triazol-3-one205

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(4-methylsulfonylphenyl)benzothiophen-2- yl]methyl]-1,2,4-triazol-3-one 206

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]- 1,2,4-triazol-3-one 207

5-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-ethyl- pyridin-2-one 208

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]- 1,2,4-triazol-3-one 209

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one 210

6-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-8-methyl- 3,4-dihydro-1H-quinolin-2-one211

6-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-methyl- 3,4-dihydroquinolin-2-one 212

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)benzothiophen-2- yl]methyl]-1,2,4-triazol-3-one213

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-piperazin-1-yl-3-pyridyl)-2- pyridyl]-1,2,4-triazol-3-one 214

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[4-(morpholine-4-carbonyl)phenyl]-2- pyridyl]-1,2,4-triazol-3-one 215

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-morpholino-3-pyridyl)-2-pyridyl]- 1,2,4-triazol-3-one 216

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(3-piperazin-1-ylphenyl)-2-pyridyl]- 1,2,4-triazol-3-one 217

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[3-(dimethylamino)-4-fluoro-phenyl]- 2-pyridyl]-1,2,4-triazol-3-one218

5-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]- 1-ethyl-pyridin-2-one 219

7-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1,4-dihydro-3,1-benzoxazin-2-one 220

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(6-piperazin-1-yl-3-pyridyl)- 2-pyridyl]-1,2,4-triazol-3-one221

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-4H-1,4-benzoxazin-3-one 222

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3- one 223

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-pyridyl]-1,2,4-triazol- 3-one 224

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3,4,5-trimethoxyphenyl)-2- pyridyl]-1,2,4-triazol-3-one 225

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(6-methoxy-3-pyridyl)-3-methyl-2- pyridyl]-1,2,4-triazol-3-one 226

4-[5-(2-amino-1,3-benzothiazol-5-yl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one 227

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(2,1,3-benzoxadiazol-5-yl)-3-methyl-2- pyridyl]-1,2,4-triazol-3-one228

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]-1,2,4-triazol-3-one 229

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzoxazol-5-yl)-3-methyl-2- pyridyl]-1,2,4-triazol-3-one 230

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one 231

4-[5-(5-acetyl-2-thienyl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro- allyl]-1,2,4-triazol-3-one 232

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-pyrazol-3-yl)phenyl]- 2-pyridyl]-1,2,4-triazol-3-one233

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1H-indazol-6-yl)-3-methyl-2-pyridyl]- 1,2,4-triazol-3-one 234

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-methylsulfonylphenyl)-2- pyridyl]-1,2,4-triazol-3-one 235

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-piperazin-1-ylphenyl)-2- pyridyl]-1,2,4-triazol-3-one 236

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [3-methyl-5-[4-(morpholine-4-carbonyl)phenyl]-2-pyridyl]-1,2,4-triazol- 3-one 237

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-morpholinophenyl)-2- pyridyl]-1,2,4-triazol-3-one 238

4-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl- 3-pyridyl]-N,N-dimethyl-benzenesulfonamide 239

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one 240

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one 241

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-3-methyl-2-pyridyl]- 1,2,4-triazol-3-one 242

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-pyridyl]-1,2,4-triazol- 3-one 243

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4- triazol-3-one 244

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2- pyridyl]-1,2,4-triazol-3-one 245

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2- pyridyl]-1,2,4-triazol-3-one 246

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)ethynyl]-3-methyl-2- pyridyl]-1,2,4-triazol-3-one 247

7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-1H-pyrido[2,3- b][1,4]oxazin-2-one 248

7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-4H-pyrido[3,2- b][1,4]oxazin-3-one 249

6-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-3,4-dihydro-1H- quinolin-2-one 250

6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl- 3-pyridyl]-3-methyl-1,4-dihydroquinazolin-2-one 251

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[1-(difluoromethyl)pyrazol-4-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one 252

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-isopropylpyrazol-4-yl)-3-methyl-2- pyridyl]-1,2,4-triazol-3-one253

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [2-methyl-3-(4-methylsulfonylphenyl)phenyl]-1,2,4- triazol-3-one 254

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [2-methyl-3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one 255

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[6-(trifluoromethyl)-3- pyridyl]phenyl]-1,2,4-triazol-3-one256

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]-2- methyl-phenyl]-1,2,4-triazol-3-one257

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)-2-methyl- phenyl]-1,2,4-triazol-3-one 258

6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-8-methyl-3,4-dihydro-1H- quinolin-2-one 259

6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-1-methyl-3,4-dihydroquinolin-2- one 260

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)-2-methyl- phenyl]-1,2,4-triazol-3-one 261

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[1-(difluoromethyl)pyrazol-4-yl]-2-methyl-phenyl]-1,2,4-triazol-3-one 262

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-isopropylpyrazol-4-yl)-2-methyl- phenyl]-1,2,4-triazol-3-one 263

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[3-(1H-1,2,4-triazol-3-yl)phenyl]phenyl]-1,2,4-triazol-3-one 264

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)phenyl]methyl]- 1,2,4-triazol-3-one 265

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[4-(4-methylsulfonylphenyl)phenyl]methyl]- 1,2,4-triazol-3-one 266

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[4-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3- one 267

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[4-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3- one 268

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[4-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one 269

6-[4-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro- 1H-quinolin-2-one 270

5-[4-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one 271

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(1-ethylpyrazol-4-yl)phenyl]methyl]- 1,2,4-triazol-3-one 272

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[3-(4-methylsulfonylphenyl)phenyl]methyl]- 1,2,4-triazol-3-one 273

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[3-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3- one 274

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[3-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one 275

6-[3-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro- 1H-quinolin-2-one 276

6-[3-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4- dihydroquinolin-2-one 277

5-[3-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one 278

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(1-ethylpyrazol-4-yl)phenyl]methyl]- 1,2,4-triazol-3-one 279

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[2-(4-methylsulfonylphenyl)phenyl]methyl]- 1,2,4-triazol-3-one 280

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[2-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3- one 281

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[2-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3- one 282

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[2-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one 283

6-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro- 1H-quinolin-2-one 284

6-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4- dihydroquinolin-2-one 285

5-[2-[[1-[2-(aminomethyl)-3,3-difluoro- allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one 286

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 287

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 288

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 289

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one 290

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[4-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one 291

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[3-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one 292

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-pyrazol-4-yl)-2-thienyl]methyl]- 1,2,4-triazol-3-one 293

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 294

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-cyclopropylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 295

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(cyclopropylmethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one 296

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(1-methylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 297

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4- [[5-(1-benzylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one 298

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one 299

5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-ethyl-pyridin-2-one 300

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-one 301

6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-methyl-3,4- dihydroquinolin-2-one 302

2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-one 303

2-(2-(aminomethyl)-3,3-difluoroallyl)-4-((5-(6-(dimethylamino)pyridin-3-yl)-3-fluorothiophen-2-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-one 304

6-(5-((1-(2-(aminomethyl)-3,3- difluoroallyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)methyl)-4- fluorothiophen-2-yl)-8-methyl-3,4-dihydroquinolin-2(1H)-one *Compounds were isolated as trifluoroacetateor ditrifluoroacetate salts as indicated in the Examples.

Experimental Example 1: Activity Evaluation with Respect to AmineOxidases

The compounds according to the present technology were evaluated interms of activity on recombinant human VAP-1 (R&D systems) by measuringthe level of hydrogen peroxide in horseradish peroxidase (HRP)-coupledreaction using Amplex Red Hydrogen Peroxide Assay Kit (Molecular Probes,Invitrogen, USA). The experiment was carried out at room temperatureusing benzylamine as a substrate. In the HRP-coupled reaction, hydrogenperoxide oxidation of 10-acetyl-3,7-dihydroxyphenoxazine (Amplex Redreagent) produces resorufin, which is a highly fluorescent compound.Briefly, the test compound was dissolved in dimethyl sulfoxide (DMSO) ata concentration of 20 mM. The dose-response assessment was made by 1:3serial dilution in DMSO, thereby creating a 8 point curve. Theconcentration of the upper part was controlled according to the efficacyof the compounds, followed by the dilution with a reaction buffersolution to obtain a final DMSO concentration of less than 1%. To eachwell of a 96 black well plate, human VAP-1 purified in 50 mM sodiumphosphate buffer solution (pH7.4) was added. The test compoundsdissolved in DMSO were incubated with the human VAP-1 enzymes at 37° C.for 30 minutes. After 30-minute incubation, each well was added with areaction mixture containing 200 uM Amplex Red reagent prepared from 50mM sodium phosphate buffer solution (pH 7.4), 1 mM benzylamine, and 1U/mL HRP. Fluorescence intensity was measured at several time pointsduring 1-2 hours using a microplate reader (Flexstation3, MolecularDevices) under the wavelength condition exciting at 544 nm and readingthe emission at 590 nm. The inhibitory effect of the compounds wasmeasured as a decrease (%) in the signal rate as compared to the controlgroup without any inhibitor (only diluted DMSO). Data was fixed to alogistic model with four variables and IC₅₀ value was calculated usingGraphPad Prism program.

In addition, the compounds according to the present technology wereevaluated in terms of activity on a recombinant human MAO-A (monoamineoxidase-A, Sigma-Aldrich) and a recombinant human MAO-B (monoamineoxidase-B, Sigma-Aldrich) by using as substrates, 0.5 mM tyramine and 1mM benzylamine, respectively, with a method similar to the activityevaluation method for recombinant human VAP-1. The compounds accordingto the present technology were also evaluated in terms of activity on arecombinant human DAO (diamine oxidase, R&D systems) by using as asubstrate 1 mM putrescine with a method similar to the activityevaluation method for recombinant human VAP-1.

The results obtained by evaluating the activity against the enzymes asabove are shown in Tables 2-5 below.

TABLE 2 Inhibitory Activity (IC₅₀, nM) Example human VAP-1 MAO-A MAO-BDAO 1 2.0 >100,000 39,000 >10,000 2 6.2 >100,000 >100,000 46,000 34.0 >100,000 25,000 19,000 4 4.2 >100,000 2,300 58,000 5 2.5 >100,0004,900 67,000 6 9.4 >100,000 >100,000 >100,000 7 9.4 >100,000 6,10010,000 8 2.2 >100,000 >100,000 10,500 9 3.5 >100,000 >100,000 7,100 107.7 >100,000 >100,000 1,200 11 1.1 >100,000 57,000 >100,000 1243 >100,000 >10,000 55,000 13 3.6 >100,000 3,600 910 14 1.4 >100,00040,000 4,100 15 3.0 >100,000 >100,000 >100,000 16 4.6 >100,000 38,0001,100 17 12 >100,000 >10,000 1,300 18 15 >100,000 >100,000 13,000 195.3 >100,000 >10,000 240 20 2.1 >100,000 >100,000 350 21 2.5 36,20018,000 6,300 22 0.8 >100,000 >100,000 >10,000 23 3.1 >100,000 >100,0008,400 24 2.7 >100,000 3,300 600 25 1.7 6,280 >10,000 1,300 260.7 >100,000 180 71 27 0.4 >100,000 350 380 28 1.2 >100,000 85 1,600 290.2 >100,000 150 200 30 0.6 >100,000 300 890 31 0.2 >100,000 870 59 321.3 >100,000 17,000 670 33 0.3 11,000 190 17 34 0.3 27,000 770 250 350.3 >100,000 33 540 36 0.1 >100,000 160 97 37 0.5 >100,000 880 860 380.4 >100,000 450 24 39 1.2 >100,000 46,000 310 40 0.3 >100,000 200 12 410.2 >100,000 470 120 42 0.3 >100,000 34 250 43 0.2 >100,000 100 22 440.3 >100,000 110 14 45 0.2 >100,000 410 200 46 0.9 >100,000 >100,000 19047 3.5 >100,000 >100,000 1,900 48 1 >100,000 31,000 61 491.6 >100,000 >100,000 490 50 1.5 >100,000 13,000 1,200 51 0.6 >100,00028,000 520 52 0.9 >100,000 23,000 300 53 1.3 >100,000 >100,000 1,710 544.9 >100,000 >100,000 480 55 6.6 >100,000 >100,000 620 56 1.6 >100,00079,600 75 57 0.9 >100,000 56,400 30 58 2.2 >100,000 >100,000 1,700 590.5 >100,000 >100,000 84 60 1.3 >100,000 >100,000 810 61 0.7 >100,00014,000 19 62 1.5 >100,000 >100,000 160 63 0.7 >100,000 16,000 110 640.4 >100,000 480 270 65 0.3 >100,000 12,000 290 66 0.6 >100,000 4,800250 67 0.9 >100,000 8,300 490 68 0.5 >100,000 55,000 2,100 691.2 >100,000 >100,000 >100,000 70 0.7 >100,000 5,800 1,500 710.8 >100,000 >100,000 >100,000 72 0.5 >100,000 1,500 57,000 730.3 >100,000 7,200 6,100 74 0.3 >100,000 7,500 6,500 750.7 >100,000 >100,000 20,000 76 1.1 >100,000 44,000 32 77 1 >100,0001,600 10 78 0.6 >100,000 9,800 57 79 0.9 >100,000 910 200 800.4 >100,000 5,300 36 81 0.4 >100,000 3,500 27 82 0.1 >100,000 3,700 1383 0.4 >100,000 >10,000 250 84 0.2 >100,000 900 7 85 0.2 >100,000 130180 86 0.1 >100,000 640 33 87 0.1 >100,000 1,100 22 88 0.3 >100,0008,200 230 89 0.6 >100,000 1900 2 90 1.3 >100,000 >100,000 30 910.5 >100,000 200 1 92 0.2 >100,000 6,200 8 93 0.3 >100,000 50 21 940.2 >100,000 860 4 95 0.6 >100,000 1,300 19 96 13 >100,000 220 >100,00097 1.3 >100,000 20,000 >10,000 98 23 >100,000 13,900 18,600 999.3 >100,000 21,000 >100,000 100 0.5 >100,000 11,000 >10,000

TABLE 3 Inhibitory Activity (IC₅₀, nM) Example human VAP-1 MAO-A MAO-BDAO 101 0.3 >100,000 67,000 21,000 102 0.4 >100,000 5,400 >10,000 1030.9 >100,000 4,200 22,000 104 0.5 >100,000 >10,000 31,000 1051.5 >100,000 6,500 >10,000 106 4.7 >100,000 >100,000 860 1073.5 >100,000 46,000 12,000 108 2.0 >10,000 >10,000 42,000 1091.4 >100,000 >100,000 84,000 110 1.3 >10,000 8,700 >100,000 1110.4 >100,000 9,400 7,200 112 0.2 >100,000 26,000 >100,000 1130.6 >100,000 2,700 19,000 114 4.9 >100,000 >100,000 970 115 0.8 >100,00010,000 11,000 116 1.4 >100,000 >10,000 >100,000 1171.1 >100,000 >100,000 7,100 118 3.5 >100,000 >100,000 40,000 1190.5 >100,000 30,000 >10,000 120 6 >100,000 >100,000 >100,000 1210.9 >100,000 40,000 >10,000 122 0.4 >100,000 25,000 54,000 1230.9 >100,000 56,000 59,000 124 11 >100,000 >100,000 >100,000 1252.5 >100,000 >100,000 >100,000 126 0.5 >100,000 760 >100,000 1270.6 >100,000 1,070 >100,000 128 0.7 >100,000 >100,000 97,000 1290.7 >100,000 311 21,000 130 0.7 >100,000 >100,000 >100,000 131 0.4 7,80012,000 >100,000 132 0.2 >100,000 >100,000 >100,000 1330.2 >100,000 >100,000 >10,000 134 0.3 >100,000 22,000 >100,000 1350.4 >100,000 >100,000 79,000 136 0.4 >100,000 >100,000 >100,000 1370.3 >100,000 >100,000 >100,000 138 0.1 >100,000 15,000 13,000 139 1.021,000 21,000 73,000 140 0.8 6,600 8,000 6,800

TABLE 4 Inhibitory Activity (IC₅₀, nM) Example human VAP-1 MAO-A MAO-BDAO 141 0.6 8,100 20,000 16,000 142 0.2 >100,000 32,000 16,000 1430.2 >100,000 6,400 >10,000 144 0.7 >100,000 >100,000 >10,000 1450.8 >100,000 >100,000 >100,000 146 1.1 >100,000 33,000 9,200 14711 >100,000 >100,000 2,600 148 0.7 >100,000 8,700 6,300 1490.6 >100,000 >100,000 >10,000 150 2.9 >100,000 2,800 >10,000 1510.3 >100,000 26,100 6,600 152 0.2 >100,000 13,400 3,500 153 1.3 >100,00029,000 36,000 154 4.0 >100,000 >100,000 21,000 155 56 >100,000 >100,00050,000 156 3.2 >100,000 17,000 9,100 157 2.3 >100,000 >100,000 >100,000158 7 >100,000 3,800 >100,000 159 5.2 >100,000 >100,000 52,000 1601.5 >100,000 15,600 5,090 161 0.2 >100,000 >100,000 54,000 1620.7 >10,000 10,000 >10,000 163 0.4 >100,000 31,000 8,400 164 2.5 4,00034,000 >10,000 165 0.5 >100,000 5,900 >10,000 1660.9 >10,000 >10,000 >10,000 167 2.1 >100,000 41,000 >10,000 1681.0 >10,000 45,000 >100,000 169 0.2 >100,000 >100,000 >100,000 1700.8 >100,000 14,000 >10,000 171 1.8 >100,000 50,000 >100,000 17213 >100,000 61,000 >100,000 173 0.3 >100,000 69,000 260 1741.3 >100,000 >100,000 29 175 0.4 >100,000 14,000 250 1760.5 >100,000 >100,000 1,100 177 1.2 >100,000 700 2,500 1780.6 >100,000 >100,000 350 179 0.3 >100,000 >100,000 290 180 0.6 >100,00061,000 1,900

TABLE 5 Inhibitory Activity (IC₅₀, nM) Example human VAP-1 MAO-A MAO-BDAO 181 2.3 >100,000 >100,000 >10,000 182 0.2 >100,000 >100,000 >100,000183 1.4 >100,000 2,100 >100,000 184 2.6 >100,000 26,000 72,000 1851.3 >100,000 28,000 >100,000 186 0.5 >100,000 >100,000 25,000 1871.1 >100,000 >100,000 8,900 188 3.4 >100,000 >100,000 7,400 1890.5 >100,000 >100,000 23,000 190 1.4 >100,000 >100,000 63,000 1910.3 >100,000 44,000 4,200 192 0.4 >100,000 56,000 22,000 1931.3 >100,000 >100,000 8,700 194 2.9 >100,000 9,200 64,000 195 2 >100,00038,000 31,000 196 1.4 >100,000 2,900 1,900 197 0.8 >100,000 18,000 2,400198 4.6 >100,000 23,000 880 199 1.7 >100,000 1,100 15,000 2001.9 >100,000 740 >100,000 201 2.8 90800 2,000 27,000 2022 >100,000 >100,000 5,600 203 1.5 >100,000 780 4,000 204 0.5 >100,00089,900 41,200 205 0.8 >100,000 >100,000 7,674 206 2.3 >100,000 14,570639 207 0.7 >100,000 >100,000 >100,000 208 2.5 89,940 42,390 >100,000209 4.3 >100,000 5,185 93,690 210 1.5 >100,000 >100,000 1,227 211 1.138,860 42,730 1,861 212 1.5 79140 >100,000 4,319 2132.5 >100,000 >100,000 1,300 214 1.7 >100,000 >100,000 940 2150.7 >100,000 >100,000 280 216 1.3 >100,000 >100,000 63 217 1.1 >100,00013,700 1,500 218 0.8 >100,000 >100,000 130 219 0.2 >100,000 68,500 47220 1.1 >100,000 >100,000 11,000 221 0.3 20,000 9,000 2,700 2221 >100,000 >100,000 4,000 223 1.5 >10,000 38,000 37,000 224 0.8 >100,0001,900 5,500 225 0.5 >100,000 1,600 14,000 226 0.5 >100,00011,000 >100,000 227 0.7 >100,000 340 4,800 228 0.6 >100,000 3,300 7,700229 0.6 >10,000 4,100 97,000 230 0.7 >100,000 77,000 24,000 231 0.240,400 1,950 3,910 232 0.5 >100,000 1,100 15,000 233 0.2 >100,000 20036,000 234 0.4 >100,000 1,800 7,500 235 1.4 >100,000 840 >100,000 2360.8 >100,000 >100,000 6,700 237 0.42 >100,000 84,000 6,100 2380.14 >100,000 1,800 310 239 2.7 >100,000 14,000 11,000 240 1 >100,00015,000 30,000 241 1.3 >100,000 6,300 25,000 242 1 >100,000 29,000 4,200243 0.9 32,700 2,200 4,600 244 0.8 >100,000 37,000 9,000 2452.7 >100,000 15,000 14,000 246 2.3 >100,000 120,000 59,000 2470.3 >100,000 >100,000 43,000 248 2.7 >100,000 14,000 >100,000 2490.9 >100,000 3,100 3,900 250 0.2 >100,000 >100,000 4,300 2511.5 >100,000 18,000 19,000 252 1 >100,000 35,000 17,000 2532.8 >100,000 >100,000 8,700 254 8 >100,000 >100,000 >100,000 2552.3 >100,000 >100,000 35,000 256 2.5 >100,000 >100,000 >100,000 2572.4 >100,000 101,000 >100,000 258 2.5 >100,000 >100,000 >100,000 2591.3 >100,000 >100,000 >100,000 260 3.7 >100,000 >100,000 >100,000 2616.5 >100,000 >100,000 >100,000 262 7.4 >100,000 >100,000 >100,000 26329 >100,000 >100,000 >100,000 264 1.3 >100,000 >100,000 >100,000 2651.4 >100,000 >100,000 >100,000 266 9.1 >100,000 >100,000 330 2671.1 >100,000 >100,000 >100,000 268 2.1 >100,000 1,870 >100,000 2691 >100,000 >100,000 71,000 270 0.6 >100,000 >100,000 >100,000 2712.2 >100,000 1,592 >100,000 272 3.2 >100,000 23,780 4,326 2731.8 >100,000 2,897 39,270 274 3.1 >100,000 125 54,080 275 0.9 >100,00025,420 5,158 276 0.5 >100,000 2,251 3,084 277 2.5 >100,000 68,620 1,811278 17 >100,000 >100,000 >100,000 279 >100 >100,000 >100,000 >100,000280 2,376 >100,000 >100,000 >100,000 281 307 >100,000 >100,000 4,858 28228 >100,000 >100,000 >100,000 283 154 >100,000 >100,000 >100,000 284148 >100,000 >100,000 66,360 285 >100 >100,000 >100,000 >100,000 286 1.42,619 3,231 2,476 287 0.7 >100,000 12,150 13,940 288 2.6 2,909 3,2273,777 289 0.6 >100,000 11,950 14,530 290 0.7 >100,000 1,188 2,377 2910.6 >100,000 3,447 6,158 292 2.7 86,170 >100,000 >100,000 2932.4 >100,000 >100,000 25,300 294 2.9 >100,000 >100,000 5,379 2950.3 >100,000 >100,000 >100,000 296 1 >100,000 >100,000 >100,000 2971.9 >100,000 >100,000 14,810 298 12 >100,000 >100,000 0.2 2991.4 >100,000 >100,000 9,679 300 1.7 >100,000 11,080 25,340 3010.5 >100,000 >100,000 2,682 302 1.1 >100,000 >100,000 19,470 3030.8 >100,000 >100,000 >100,000 304 0.7 >100,000 >100,000 12,570

From the results of Tables 2-5 above, it can be seen that the compoundsaccording to the present technology have excellent inhibitory activityon VAP-1 among various amine oxidases.

Para. A. A compound of Formula X

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

n is 0, 1 or 2; and

A is an aryl group or a heterocyclic group, wherein said heterocyclicgroup has 1 to 5 heteroatom ring members chosen from O, N, or S, andsaid heterocyclic group is aromatic or non-aromatic; and wherein saidaryl group or said heterocyclic group is optionally substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R; and

R is a substituted or unsubstituted cyclic ring, optionally containing 1to 5 heteroatom ring members chosen from O, N, or S, and said cyclicring is aromatic or non-aromatic.

Para. B. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. A, wherein A is aryl optionallysubstituted with one or two substituents selected from the groupconsisting of C₁₋₃ alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R.

Para. C. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. B, wherein A is phenyl substitutedwith one or two substituents selected from the group consisting of C₁₋₃alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R.

Para. D. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. A, wherein A is a heterocyclic grouphaving 1 to 5 heteroatom ring members chosen from O, N, or S; saidheterocyclic group is aromatic or non-aromatic; and said heterocyclicgroup is optionally substituted with one or two substituents selectedfrom the group consisting of C₁₋₃ alkyl, halogen, benzyloxy, —R,—CH═CH—R, and —C≡C—R.

Para. E. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. D, wherein A is a heteroaryl grouphaving 1 to 5 heteroatom ring members chosen from O, N, or S; and saidheteroaryl group is optionally substituted with one or two substituentsselected from the group consisting of C₁₋₃ alkyl, halogen, benzyloxy,—R, —CH═CH—R, and —C≡C—R.

Para. F. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. E, wherein A is pyridine, pyrazine, orthiophene, wherein A is optionally substituted with one or twosubstituents selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C≡C—R.

Para. G. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. A-F, wherein R is a cyclicring optionally containing 1-5 heteroatom ring members, and said cyclicring is optionally substituted with one to three substituents selectedfrom the group consisting of halogen, C₁₋₆ alkyl, difluoromethyl,trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy, amino, mono- ordi-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, pyrrolidinonyl,and pyrrolidinyl.

Para. H. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. A-G, wherein n is 0.

Para. I. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. A-G, wherein n is 1.

Para. J. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. A-G, wherein n is 2.

Para. K. A compound of Formula Y

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

n is 0, 1 or 2;

A is an aryl or heteroaryl group selected from the group consisting ofphenyl, pyridine, pyrazine, thiophene, and benzothiophene;

wherein said aryl or heteroaryl group is optionally substituted with oneor two substituents selected from the group consisting of C₁₋₃ alkyl,halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R;

wherein said R is a cyclic ring selected from the group consisting ofbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine,imidazole, pyrazole, benzodioxole, benzoxadiazole, benzothiazole,indazole, 1,3-dihydroindol-2-one, quinolin-2-one,3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,3,4-dihydro-1,4-benzoxazine, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene;

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, pyrrolidinonyl,and pyrrolidinyl.

Para. L. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein n is 0 or 1, and A isphenyl, pyridine or thiophene, optionally substituted with one or twosubstituents selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C≡C—R.

Para. M. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein said aryl or heteroarylgroup is substituted with one or two substituents selected from thegroup consisting of C₁₋₃ alkyl, halogen, and —R.

Para. N. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. M, wherein said R is a cyclic ringselected from the group consisting of benzene, pyridine, pyridin-2-one,pyrazole and 3,4-dihydroquinolin-2-one, said cyclic ring is optionallysubstituted with one to three substituents selected from the groupconsisting of halogen, C₁₋₆ alkyl, difluoromethyl, trifluoromethyl, C₁₋₆alkoxy, amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino,C₁₋₆ alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, C₁₋₆ alkylcarbonyl,morpholinylcarbonyl, piperazinyl, acetylpiperazinyl, morpholinyl,pyrazolyl, triazolyl, and pyrrolidinyl.

Para. O. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. N, wherein said cyclic ring issubstituted with a substituent selected from the group consisting ofC₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆ alkylamino, and piperazinyl.

Para. P. The compound or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K,

wherein n is 0;

A is phenyl;

wherein said phenyl is substituted with one or two substituents selectedfrom the group consisting of halogen and —R;

wherein said R is a cyclic ring selected from the group consisting ofbenzene, pyridine, 3,4-dihydroquinolin-2-one and pyrazole; and

wherein said cyclic ring is substituted with a substituent selected fromthe group consisting of C₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆alkylamino, and piperazinyl.

Para. Q. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein

n is 0;

A is pyridine;

wherein said pyridine is substituted with one or two substituentsselected from the group consisting of C₁₋₃ alkyl, halogen, and —R;

wherein said R is a cyclic ring selected from the group consisting ofbenzene, pyridine, 3,4-dihydroquinolin-2-one and pyrazole; and

wherein said cyclic ring is substituted with a substituent selected fromthe group consisting of C₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆alkylamino, and piperazinyl.

Para. R. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein

n is 0;

A is thiophene;

wherein said thiophene is substituted with one or two cyclic ringsselected from the group consisting of benzene, pyridine, pyridin-2-one,3,4-dihydroquinolin-2-one and pyrazole; and

wherein said cyclic ring is substituted with a substituent selected fromthe group consisting of C₁₋₆ alkyl, C₁₋₆ alkylsulfonyl, di-C₁₋₆alkylamino, and piperazinyl.

Para. S. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein A is phenyl optionallysubstituted with one or two substituents selected from the groupconsisting of C₁₋₃ alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R.

Para. T. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. S, wherein A is phenyl substitutedwith —R.

Para. U. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. T, wherein —R is a cyclic ringselected from the group consisting of benzene, pyridine, pyridin-2-one,pyrazole, benzodioxole, and 3,4-dihydroquinolin-2-one;

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinonyl.

Para. V. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein A is pyridine substitutedwith —R.

Para. W. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. V, wherein —R is a cyclic ringselected from the group consisting of benzene, pyridine, pyridin-2-one,pyrimidine, pyrazole, benzodioxole, benzoxadiazole, benzothiazole,indazole, 2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene.

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinonyl.

Para. X. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein A is thiophene substitutedwith —R.

Para. Y The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. X, wherein —R is a cyclic ringselected from the group consisting of benzene, pyridine,tetrahydropyridine, pyridin-2-one, pyrimidine, imidazole, pyrazole,benzodioxole, benzoxadiazole, benzothiazole, indazole,1,3-dihydroindol-2-one, quinolin-2-one, 3,4-dihydroisoquinolin-1-one,3,4-dihydroquinolin-2-one, 2,3-dihydro-1,4-benzoxazine,1,4-dihydro-3,1-benzoxazin-2-one, 5,6,7,8-tetrahydronaphthyridine,triazolo[1,5-a]pyridine, pyrido[2,3-b][1,4]oxazin-2-one, and1,4-dihydroquinazolin-2-one;

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

Para. Z. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. K, wherein A is benzothiophenesubstituted with —R.

Para. AA. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. Z, wherein —R is a cyclic ringselected from the group consisting of benzene, pyridine, pyridin-2-one,pyrazole, benzodioxole, and 3,4-dihydroquinolin-2-one, wherein saidcyclic ring is optionally substituted with one to three substituentsselected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

Para. AB. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. S-AA, wherein n is 0.

Para. AC. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. S-AA, wherein n is 1.

Para. AD. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. S-AA, wherein n is 2.

Para. AE. A compound of Formula 12

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl group or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

Para. AF. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AE, wherein R¹ is hydrogen.

Para. AG. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AE, wherein R¹ is halogen.

Para. AH. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AE, wherein R¹ is C₁₋₆ alkyl.

Para. AI. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. AE-AH, wherein R² is asubstituted or unsubstituted aryl group.

Para. AJ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AI, wherein R² is substituted orunsubstituted phenyl.

Para. AK. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AI, wherein R² is phenyl substitutedwith triazolyl, C₁₋₆ alkylsulfonyl, or piperazinyl.

Para. AL. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AI, wherein R² is benzodioxole or3,4-dihydroquinolin-2-one, wherein said 3,4-dihydroquinolin-2-one isoptionally substituted with C₁₋₆ alkyl.

Para. AM. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. AE-AH, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. AN. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AM, wherein R² is substituted orunsubstituted pyridine.

Para. AO. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AN, wherein R² is pyridine substitutedwith trifluoromethyl or mono- or di-C₁₋₆ alkylamino.

Para. AP. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AM, wherein R² is substituted orunsubstituted pyrazole.

Para. AQ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AP, wherein R² is pyrazole substitutedwith C₁₋₆ alkyl or difluoromethyl.

Para. AR. A compound of Formula 13

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aralkoxy group, a substituted orunsubstituted aryl group, or a substituted or unsubstituted heterocyclicgroup, wherein said heterocyclic group has 1 to 5 heteroatom ringmembers chosen from O, N, or S, and said heterocyclic group is aromaticor non-aromatic.

Para. AS. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AR, wherein R¹ is hydrogen.

Para. AT. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AR, wherein R¹ is halogen.

Para. AU. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AR, wherein R¹ is C₁₋₆ alkyl.

Para. AV. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. AR-AU, wherein R² is asubstituted or unsubstituted aryl group.

Para. AW. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AV, wherein R² is substituted orunsubstituted phenyl.

Para. AX. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AW, wherein R² is phenyl substitutedwith C₁₋₆ alkylsulfonyl or piperazinyl.

Para. AY The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AV, wherein R² is benzodioxole or3,4-dihydroquinolin-2-one, wherein said 3,4-dihydroquinolin-2-one isoptionally substituted with C₁₋₆ alkyl.

Para. AZ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. AR-AU, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. BA. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AZ, wherein R² is substituted orunsubstituted pyridine.

Para. BB. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BA, wherein R² is pyridine substitutedwith mono- or di-C₁₋₆ alkylamino.

Para. BC. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. AZ, wherein R² is substituted orunsubstituted pyrazole.

Para. BD. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BC, wherein R² is pyrazole substitutedwith C₁₋₆ alkyl.

Para. BE. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. AR-AU, wherein R² issubstituted or unsubstituted pyridin-2-one.

Para. BF. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BE, wherein R² is pyridin-2-onesubstituted with C₁₋₆ alkyl.

Para. BG. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. AR-AU, wherein R² issubstituted or unsubstituted aralkoxy group.

Para. BH. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BG, wherein R² is substituted orunsubstituted benzyloxy.

Para. BI. A compound of Formula 14

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

Para. BJ. The compound of Para. BI of Formula 14a

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

Para. BK. The compound of Para. BI of Formula 14b

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

Para. BL. The compound of Para. BI of Formula 14c

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

Para. BM. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BI-BL, wherein R¹ ishydrogen.

Para. BN. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BI-BL, wherein R¹ ishalogen.

Para. BO. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BI-BL, wherein R¹ is C₁₋₆alkyl.

Para. BP. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BI-BL, wherein R² is asubstituted or unsubstituted aryl group.

Para. BQ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BP, wherein R² is substituted orunsubstituted phenyl.

Para. BR. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BQ, wherein R² is phenyl substitutedwith one to three substituents selected from the group consisting ofwith halogen, C₁₋₆ alkoxy, mono- or di-C₁₋₆ alkylamino, mono- or di-C₁₋₆alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, morpholinylcarbonyl,piperazinyl, morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, andpyrrolidinonyl.

Para. BS. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BP, wherein R² is benzodioxole,benzoxadiazole, benzothiazole, indazole, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,1,4-dihydroquinazolin-2-one, 3,4-dihydroquinolin-2-one, or benzoxazole,wherein R² is optionally substituted with C₁₋₆ alkyl or amino.

Para. BT. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BI-BO, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. BU. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BT, wherein R² is substituted orunsubstituted pyridine.

Para. BV. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BU, wherein R² is pyridine substitutedwith C₁₋₆ alkoxy, trifluoromethyl, piperazinyl, morpholinyl, or mono- ordi-C₁₋₆ alkylamino.

Para. BW. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BT, wherein R² is pyrimidine,1H-pyrrolo[2,3-b]pyridine, pyrazole, or thiophene, wherein R² isoptionally substituted with C₁₋₆ alkyl, difluoromethyl, C₁₋₆ alkoxy-C₁₋₆alkylamino, or C₁₋₆ alkylcarbonyl.

Para. BX. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BI-BO, wherein R² issubstituted or unsubstituted pyridin-2-one.

Para. BY The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BX, wherein R² is pyridin-2-onesubstituted with C₁₋₆ alkyl.

Para. BZ. A compound of Formula 15

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S group.

Para. CA. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BZ, wherein R¹ is hydrogen.

Para. CB. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. BZ, wherein R¹ is C₁₋₆ alkyl.

Para. CC. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BZ-CB, wherein R² is asubstituted or unsubstituted aryl group.

Para. CD. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CC, wherein R² is substituted orunsubstituted phenyl.

Para. CE. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CC, wherein R² is2,3-dihydro-1,4-benzoxazine or 3,4-dihydroquinolin-2-one, wherein said3,4-dihydroquinolin-2-one is optionally substituted with C₁₋₆ alkyl.

Para. CF. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. BZ-CB, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. CG. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CF, wherein R² is substituted orunsubstituted pyridine.

Para. CH. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CG, wherein R² is pyridine substitutedwith morpholinyl or mono- or di-C₁₋₆ alkylamino.

Para. CI. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CF, wherein R² is2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, or pyrazole, wherein said pyrazole isoptionally substituted with C₁₋₆ alkyl.

Para. CJ. A compound of Formula 16

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

Para. CK. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CJ, wherein R² is a substituted orunsubstituted aryl group.

Para. CL. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CK, wherein R² is substituted orunsubstituted phenyl.

Para. CM. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CL, wherein R² is phenyl substitutedwith C₁₋₆ alkylsulfonyl or piperazinyl.

Para. CN. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CK, wherein R² is benzodioxole or3,4-dihydroquinolin-2-one, wherein said 3,4-dihydroquinolin-2-one isoptionally substituted with C₁₋₆ alkyl.

Para. CO. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CJ, wherein R² is a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

Para. CP. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CO, wherein R² is substituted orunsubstituted pyridine.

Para. CQ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CQ, wherein R² is pyridine substitutedwith trifluoromethyl or mono- or di-C₁₋₆ alkylamino.

Para. CR. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CO, wherein R² is substituted orunsubstituted pyrazole.

Para. CS. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CR, wherein R² is pyrazole substitutedwith C₁₋₆ alkyl.

Para. CT. A compound of Formula 17

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

Para. CU. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CT, wherein R¹ is hydrogen.

Para. CV. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CT, wherein R¹ is halogen.

Para. CW. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CT, wherein R¹ is C₁₋₆ alkyl.

Para. CX. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. CT-CW, wherein R² is asubstituted or unsubstituted aryl group.

Para. CY The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CX, wherein R² is substituted orunsubstituted phenyl.

Para. CZ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CY, wherein R² is phenyl substitutedwith one to three substituents selected from the group consisting ofC₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkylsulfonyl, mono- or di-C₁₋₆alkylaminosulfonyl, mono- or di-C₁₋₆ alkylaminocarbonyl,morpholinylcarbonyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl,piperazinyl, and acetylpiperazinyl.

Para. DA. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. CX, wherein R² is3,4-dihydroisoquinolin-1-one, quinolin-2-one,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 1,4-dihydroquinazolin-2-one,benzothiazole, benzoxadiazole, indazole, benzodioxole,1,3-dihydroindol-2-one, or 3,4-dihydroquinolin-2-one; wherein R² isoptionally substituted with C₁₋₆ alkyl, C₁₋₆ alkylcarbonylamino, orhalogen.

Para. DB. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. CT-CW, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. DC. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DB, wherein R² is substituted orunsubstituted pyridine.

Para. DD. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DC, wherein R² is pyridine substitutedwith one to three substituents selected from the group consisting ofhalogen, trifluoromethyl, C₁₋₆ alkoxy, piperazinyl and mono- or di-C₁₋₆alkylamino.

Para. DE. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DB, wherein R² is substituted orunsubstituted pyrazole.

Para. DF. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DE, wherein R² is pyrazole substitutedwith C₁₋₆ alkyl, difluoromethyl, benzyl, (cycloalkyl)alkyl,alkylsulfonyl, or cycloalkylsulfonyl.

Para. DG. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DB, wherein R² is5,6,7,8-tetrahydronaphthyridine, pyrimidine, imidazole, ortriazolo[1,5-a]pyridine; wherein R² is optionally substituted with oneto three substituents selected from the group consisting of halogen,C₁₋₆ alkyl, C₁₋₆ alkoxy, amino, and C₁₋₆ alkoxy-C₁₋₆ alkylamino.

Para. DH. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DG, wherein R² is[1,2,4]triazolo[1,5-a]pyridine.

Para. DI. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. CT-CW, wherein R² istetrahydropyridine or pyridin-2-one, wherein said tetrahydropyridine andsaid pyridin-2-one are optionally substituted with C₁₋₆ alkyl or C₁₋₆alkylcarbonyl.

Para. DJ. A compound of Formula 18

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

Para. DK. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DJ, wherein R¹ is hydrogen.

Para. DL. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DJ, wherein R¹ is halogen.

Para. DM. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DJ, wherein R¹ is C₁₋₆ alkyl.

Para. DN. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. DJ-DM, wherein R² is asubstituted or unsubstituted aryl group.

Para. DO. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DM, wherein R² is substituted orunsubstituted phenyl.

Para. DP. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DM, wherein R² is2,3-dihydro-1,4-benzoxazine or 3,4-dihydroquinolin-2-one.

Para. DQ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. DJ-DM, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. DR. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DQ, wherein R² is substituted orunsubstituted pyridine.

Para. DS. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DR, wherein R² is pyridine substitutedwith morpholinyl or mono- or di-C₁₋₆ alkylamino.

Para. DT. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DQ, wherein R² is substituted orunsubstituted pyrazole.

Para. DU. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DT, wherein R² is pyrazole substitutedwith C₁₋₆ alkyl.

Para. DV The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DQ, wherein R² is2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,or pyrido[3,2-b][1,4]oxazin-3-one.

Para. DW. A compound of Formula 19

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members chosen from O, N, or S.

Para. DX. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DW, wherein R¹ is hydrogen.

Para. DY The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DW, wherein R¹ is halogen.

Para. DZ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. DW, wherein R¹ is C₁₋₆ alkyl.

Para. EA. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. DW-DZ, wherein R² is asubstituted or unsubstituted aryl group.

Para. EB. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EA, wherein R² is substituted orunsubstituted phenyl.

Para. EC. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EB, wherein R² is phenyl substitutedwith C₁₋₆ alkylsulfonyl or piperazinyl.

Para. ED. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EA, wherein R² is benzodioxole or3,4-dihydroquinolin-2-one; wherein R² is optionally substituted withC₁₋₆ alkyl.

Para. EE. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. DW-DZ, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. EF. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EE, wherein R² is substituted orunsubstituted pyridine.

Para. EG. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EF, wherein R² is pyridine substitutedwith trifluoromethyl or mono- or di-C₁₋₆ alkylamino.

Para. EH. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EE, wherein R² is substituted orunsubstituted pyrazole.

Para. EI. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EH, wherein R² is pyrazole substitutedwith C₁₋₆ alkyl.

Para. EJ. A compound of Formula 20

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;

wherein

R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and

R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heterocyclic group, wherein said heterocyclic group has 1to 5 heteroatom ring members chosen from O, N, or S, and saidheterocyclic group is aromatic or non-aromatic.

Para. EK. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EJ, wherein R¹ is hydrogen.

Para. EL. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EJ, wherein R¹ is halogen.

Para. EM. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EJ, wherein R¹ is C₁₋₆ alkyl.

Para. EN. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. EJ-EM, wherein R² is asubstituted or unsubstituted aryl group.

Para. EO. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EN, wherein R² is substituted orunsubstituted phenyl.

Para. EP. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EO, wherein R² is phenyl substitutedwith C₁₋₆ alkylsulfonyl or piperazinyl.

Para. EQ. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EN, wherein R² is benzodioxole or3,4-dihydroquinolin-2-one; wherein R² is optionally substituted withC₁₋₆ alkyl.

Para. ER. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. EJ-EM, wherein R² is asubstituted or unsubstituted heteroaryl group, wherein said heteroarylgroup has 1 to 5 heteroatom ring members chosen from O, N, or S.

Para. ES. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. ER, wherein R² is substituted orunsubstituted pyridine.

Para. ET. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. ES, wherein R² is pyridine substitutedwith trifluoromethyl or mono- or di-C₁₋₆ alkylamino.

Para. EU. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. ER, wherein R² is substituted orunsubstituted pyrazole.

Para. EV The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EU, wherein R² is pyrazole substitutedwith C₁₋₆ alkyl.

Para. EW. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of any one of Paras. EJ-EM, wherein R² is asubstituted or unsubstituted pyridine-2-one.

Para. EX. The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. EW, wherein R² is pyridine-2-onesubstituted with C₁₋₆ alkyl.

Para. EY The compound, or a stereoisomer thereof or a pharmaceuticallyacceptable salt thereof, of Para. A, which is selected from the groupconsisting of:

-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-fluorophenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3-bromophenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(3,4-difluorophenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-3-fluoro-phenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-fluoro-phenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-methyl-phenyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(4-bromo-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(2-bromo-4-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-methyl-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-4-methyl-3-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-5-methyl-3-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromo-3-fluoro-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(6-bromo-3-methyl-2-pyridyl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-(5-bromopyrazin-2-yl)-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1,2,4-triazol-3-one;-   6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-3-fluoro-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-3-fluoro-phenyl]-1,2,4-triazol-3-one;-   6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-fluoro-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-3-fluoro-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-fluoro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-fluoro-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-fluoro-phenyl]-1,2,4-triazol-3-one;-   6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-fluoro-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-fluoro-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-3-pyridyl]-1,2,4-triazol-3-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-[6-(dimethylamino)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1,3-benzodioxol-5-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   6-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-4-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[4-(1-ethylpyrazol-4-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-methylsulfonylphenyl)-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(4-piperazin-1-ylphenyl)-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[6-(dimethylamino)-3-pyridyl]-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1,3-benzodioxol-5-yl)-4-pyridyl]-1,2,4-triazol-3-one;-   6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[4-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(1-ethylpyrazol-4-yl)-4-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-(4-methylsulfonylphenyl)-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-methyl-6-[6-(trifluoromethyl)-3-pyridyl]-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[6-(dimethylamino)-3-pyridyl]-5-methyl-3-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(1,3-benzodioxol-5-yl)-5-methyl-3-pyridyl]-1,2,4-triazol-3-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-3-methyl-2-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-fluoro-5-[6-(trifluoromethyl)-3-pyridyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-fluoro-3-pyridyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-methylsulfonylphenyl)-pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(4-piperazin-1-ylphenyl)pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(trifluoromethyl)-3-pyridyl]pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[6-(dimethylamino)-3-pyridyl]pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzodioxol-5-yl)pyrazin-2-yl]-1,2,4-triazol-3-one;-   6-[5-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]pyrazin-2-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-ethylpyrazol-4-yl)pyrazin-2-yl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-benzyloxyphenyl)methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-2-thienyl)methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(4-bromo-2-thienyl)methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[(5-bromo-3-methyl-2-thienyl)methyl]-1,2,4-triazol-3-one;-   4-[[5-(4-acetylphenyl)-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-methyl    sulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N,N-dimethyl-benzenesulfonamide;-   4-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N-methyl-benzamide;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3,4,5-trimethoxyphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(3-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   4-[[5-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-morpholine-4-carbonyl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-pyrazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-methoxy-3-pyridyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(6-piperazin-1-yl-3-pyridyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-5-fluoro-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-aminopyrimidin-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-ethoxypyrimidin-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2-chloro-3-methyl-imidazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-pyridin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-ethyl-pyridin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-isopropyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-indazol-6-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-([1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(2,1,3-benzoxadiazol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-7-fluoro-indolin-2-one;-   N-[6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,3-benzothiazol-2-yl]acetamide;-   7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-2H-isoquinolin-1-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-methyl-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-8-fluoro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4H-1,4-benzoxazin-3-one;-   7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   7-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-4-methyl-1,4-benzoxazin-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methyl    sulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-methylsulfonylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-methyl-5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-methyl-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one;-   7-[(E)-2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]vinyl]-1H-pyrido[2,3-b][1,4]oxazin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-3,4-dihydro-1H-quinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-1H-pyrido[2,3-b][1,4]oxazin-2-one;-   7-[2-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]ethynyl]-4H-pyrido[3,2-b][1,4]oxazin-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-(2-thienyl)ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-methyl    sulfonylphenyl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(4-piperazin-1-ylphenyl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(trifluoromethyl)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-[6-(dimethylamino)-3-pyridyl]-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1,3-benzodioxol-5-yl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[5-[2-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]ethyl]-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-[5-(1-ethylpyrazol-4-yl)-2-thienyl]ethyl]-1,2,4-triazol-3-one;-   3-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-N,N-dimethyl-benzamide;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-2-thienyl]-3-methyl-1,4-dihydroquinazolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-isopropylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3-methyl-1,4-dihydroquinazolin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-isopropyl-pyridin-2-one;-   4-[[4-[4-(4-acetylpiperazin-1-yl)phenyl]-2-thienyl]methyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-8-fluoro-1H-quinolin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-methyl-pyridin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-3,4-dihydro-1H-quinolin-2-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-3-thienyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[1-(difluoromethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-isopropylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-[6-(trifluoromethyl)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-6-yl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[6-(1-ethylpyrazol-4-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-methylsulfonylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(4-piperazin-1-ylphenyl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   5-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[6-(dimethylamino)-3-pyridyl]benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzothiophen-5-yl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)benzothiophen-2-yl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-piperazin-1-yl-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[4-(morpholine-4-carbonyl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(6-morpholino-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-(3-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[6-[3-(dimethylamino)-4-fluoro-phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   5-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1-ethyl-pyridin-2-one;-   7-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-pyridyl]-1,4-dihydro-3,1-benzoxazin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(6-piperazin-1-yl-3-pyridyl)-2-pyridyl]-1,2,4-triazol-3-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-4H-1,4-benzoxazin-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2-methoxyethylamino)pyrimidin-5-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3,4,5-trimethoxyphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(6-methoxy-3-pyridyl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   4-[5-(2-amino-1,3-benzothiazol-5-yl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(2,1,3-benzoxadiazol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1,3-benzoxazol-5-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   4-[5-(5-acetyl-2-thienyl)-3-methyl-2-pyridyl]-2-[2-(aminomethyl)-3,3-difluoro-allyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-pyrazol-3-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1H-indazol-6-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-methylsulfonylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(3-piperazin-1-ylphenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[4-(morpholine-4-carbonyl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-(4-morpholinophenyl)-2-pyridyl]-1,2,4-triazol-3-one;-   4-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-N,N-dimethyl-benzenesulfonamide;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[3-(1H-1,2,4-triazol-3-yl)phenyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(1-methylpyrazol-4-yl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-[6-(dimethylamino)-3-pyridyl]ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-methyl-5-[2-(6-morpholino-3-pyridyl)ethynyl]-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[2-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)ethynyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-1H-pyrido[2,3-b][1,4]oxazin-2-one;-   7-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-4H-pyrido[3,2-b][1,4]oxazin-3-one;-   6-[2-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]ethynyl]-3,4-dihydro-1H-quinolin-2-one;-   6-[6-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-5-methyl-3-pyridyl]-3-methyl-1,4-dihydroquinazolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[1-(difluoromethyl)pyrazol-4-yl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-(1-isopropylpyrazol-4-yl)-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-(4-methylsulfonylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-(4-piperazin-1-ylphenyl)phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[6-(trifluoromethyl)-3-pyridyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[6-(dimethylamino)-3-pyridyl]-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1,3-benzodioxol-5-yl)-2-methyl-phenyl]-1,2,4-triazol-3-one;-   6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[3-[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]-2-methyl-phenyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-ethylpyrazol-4-yl)-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-[1-(difluoromethyl)pyrazol-4-yl]-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[3-(1-isopropylpyrazol-4-yl)-2-methyl-phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[2-methyl-3-[3-(1H-1,2,4-triazol-3-yl)phenyl]phenyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   6-[4-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   5-[4-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   6-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4-dihydroquinolin-2-one;-   5-[3-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(1-ethylpyrazol-4-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(4-methylsulfonylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(4-piperazin-1-ylphenyl)phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-[6-(dimethylamino)-3-pyridyl]phenyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[2-(1,3-benzodioxol-5-yl)phenyl]methyl]-1,2,4-triazol-3-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-8-methyl-3,4-dihydro-1H-quinolin-2-one;-   6-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-methyl-3,4-dihydroquinolin-2-one;-   5-[2-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[4-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[4-[3-(1-ethylpyrazol-4-yl)phenyl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[4-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[5-[3-(1-ethylpyrazol-4-yl)phenyl]-3-methyl-2-pyridyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1H-pyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-cyclopropylsulfonylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-[1-(cyclopropylmethyl)pyrazol-4-yl]-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-methylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-benzylpyrazol-4-yl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[3-fluoro-5-(4-piperazin-1-ylphenyl)-2-thienyl]methyl]-1,2,4-triazol-3-one;-   5-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-ethyl-pyridin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1,3-benzodioxol-5-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-one;-   6-[5-[[1-[2-(aminomethyl)-3,3-difluoro-allyl]-5-oxo-1,2,4-triazol-4-yl]methyl]-4-fluoro-2-thienyl]-1-methyl-3,4-dihydroquinolin-2-one;-   2-[2-(aminomethyl)-3,3-difluoro-allyl]-4-[[5-(1-ethylpyrazol-4-yl)-3-fluoro-2-thienyl]methyl]-1,2,4-triazol-3-one;-   2-(2-(aminomethyl)-3,3-difluoroallyl)-4-((5-(6-(dimethylamino)pyridin-3-yl)-3-fluorothiophen-2-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one;    and-   6-(5-((1-(2-(aminomethyl)-3,3-difluoroallyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)methyl)-4-fluorothiophen-2-yl)-8-methyl-3,4-dihydroquinolin-2(1H)-one;

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

Para. EZ. A pharmaceutical composition comprising the compound accordingto any one of Paras. A-EY, or a stereoisomer thereof, or apharmaceutically acceptable salt thereof, and at least onepharmaceutically acceptable excipient

Para. FA. A method of inhibiting vascular adhesion protein (VAP-1),comprising administering to a mammal, a therapeutically effective amountof the compound, or a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof according to any one of Paras. A-EY

Para. FB. A method of treating NASH in a subject in need thereof, themethod comprising administering to the subject a therapeuticallyeffective amount of the compound according to any one of Paras. A-EY, ora stereoisomer thereof, or a pharmaceutically acceptable salt thereof,or a therapeutically effective amount of the pharmaceutical compositionaccording to Para. EZ.

Para. FC. Use of the compound according to any one of Paras. A-EY, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, forthe manufacture of a medicament for the treatment of NASH.

Para. FD. A compound according to any one of Paras. A-EY, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse in treating NASH.

Para. FE. A compound according to any one of Paras. A-EY, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse as a medicament for the treatment of NASH.

Para. FF. A composition according to Para. EZ for use in treating NASH.

Para. FG. A compound according to any one of Paras. A-EY, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse in inhibiting VAP-1.

Para. FH. A compound according to any one of Paras. A-EY, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse as a medicament for the inhibition of VAP-1.

Para. FI. A composition according to Para. EZ for use in inhibitingVAP-1.

Para. FJ. A method of treating a disease mediated by VAP-1 in a subjectin need thereof, the method comprising administering to the subject atherapeutically effective amount of the compound according to any one ofParas. A-EY, or a stereoisomer thereof, or a pharmaceutically acceptablesalt thereof, or a therapeutically effective amount of thepharmaceutical composition according to Para. EZ.

Para. FK. The method of Para. FJ, wherein the disease mediated by VAP-1is selected from the group consisting of lipid and lipoproteindisorders, conditions and diseases which result from chronic fatty andfibrotic degeneration of organs due to accumulated lipid andspecifically triglyceride accumulation and subsequent activation ofprofibrotic pathways, Type I or Type II Diabetes and clinicalcomplications of Type I and Type II Diabetes, chronic intrahepatic orsome forms of extrahepatic cholestatic conditions, liver fibrosis, acuteintraheptic cholestatic conditions, obstructive or chronic inflammatorydisorders that arise out of improper bile composition, gastrointestinalconditions with a reduced uptake of dietary fat and fat-soluble dietaryvitamins, inflammatory bowel diseases, obesity and metabolic syndrome(combined conditions of dyslipidemia, diabetes and abnormally highbody-mass index), persistent infections by intracellular bacteria orparasitic protozoae, non-malignant hyperproliferative disorders,malignant hyperproliferative disorders, colon adenocarcinoma andhepatocellular carcinoma in particular, liver steatosis and associatedsyndromes, Hepatitis B infection, Hepatitis C infection and/or ofcholestatic and fibrotic effects that are associated withalcohol-induced cirrhosis or with viral-borne forms of hepatitis, liverfailure or liver malfunction as an outcome of chronic liver diseases orof surgical liver resection, acute myocardial infarction, acute stroke,thrombosis which occurs as an endpoint of chronic obstructiveatherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, andcerebral infarction, individually or any combination thereof.

Para. FL. A compound according to any one of Paras. A-EY, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse in treating a disease mediated by VAP-1.

Para. FM. A compound according to any one of Paras. A-EY, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof, foruse as a medicament for the treatment of a disease mediated by VAP-1.

Para. FN. The compound for use of Para. FL or Para. FM, wherein thedisease mediated by VAP-1 is selected from the group consisting of lipidand lipoprotein disorders, conditions and diseases which result fromchronic fatty and fibrotic degeneration of organs due to accumulatedlipid and specifically triglyceride accumulation and subsequentactivation of profibrotic pathways, Type I or Type II Diabetes andclinical complications of Type I and Type II Diabetes, chronicintrahepatic or some forms of extrahepatic cholestatic conditions, liverfibrosis, acute intraheptic cholestatic conditions, obstructive orchronic inflammatory disorders that arise out of improper bilecomposition, gastrointestinal conditions with a reduced uptake ofdietary fat and fat-soluble dietary vitamins, inflammatory boweldiseases, obesity and metabolic syndrome (combined conditions ofdyslipidemia, diabetes and abnormally high body-mass index), persistentinfections by intracellular bacteria or parasitic protozoae,non-malignant hyperproliferative disorders, malignant hyperproliferativedisorders, colon adenocarcinoma and hepatocellular carcinoma inparticular, liver steatosis and associated syndromes, Hepatitis Binfection, Hepatitis C infection and/or of cholestatic and fibroticeffects that are associated with alcohol-induced cirrhosis or withviral-borne forms of hepatitis, liver failure or liver malfunction as anoutcome of chronic liver diseases or of surgical liver resection, acutemyocardial infarction, acute stroke, thrombosis which occurs as anendpoint of chronic obstructive atherosclerosis, osteoarthritis,rheumatoid arthritis, psoriasis, and cerebral infarction, individuallyor any combination thereof.

Para. FO. A method of preparing a compound of Formula 1aa, or astereoisomer thereof, or a pharmaceutically acceptable salt thereof,

the method comprising

(a) reacting a compound of Formula 2 with a compound of Formula 3a or acompound of Formula 3b to obtain a compound of Formula 1a

wherein

Boc is an amine protecting group;

n is 0, 1, or 2;

A′ is aryl or heteroaryl group selected from the group consisting ofphenyl, pyridine, pyrazine, thiophene, and benzothiophene; wherein saidaryl or heteroaryl group is optionally substituted with C₁₋₃ alkyl orhalogen;

Z is boronic acid (B(OH)₂) or boronic acid pinacol ester;

R′ is —R, —CH═CH—R, or —C≡C—R; and

R is a substituted or unsubstituted cyclic ring, optionally containing 1to 5 heteroatom ring members chosen from O, N, or S, and said cyclicring is aromatic or non-aromatic; and

(b) removing Boc from the compound of Formula 1a under reactionconditions to obtain the compound of Formula 1aa, or the stereoisomerthereof, or the pharmaceutically acceptable salt thereof.

Para. FP. The method of Para. FO, wherein the cyclic ring is selectedfrom the group consisting of benzene, pyridine, tetrahydropyridine,pyridin-2-one, pyrimidine, imidazole, pyrazole, benzodioxole,benzoxadiazole, benzothiazole, indazole, 1,3-dihydroindol-2-one,quinolin-2-one, 3,4-dihydroisoquinolin-1-one, 3,4-dihydroquinolin-2-one,3,4-dihydro-1,4-benzoxazine, 2,3-dihydro-1,4-benzoxazine,1,4-benzoxazin-3-one, 1,4-dihydro-3,1-benzoxazin-2-one,5,6,7,8-tetrahydronaphthyridine, triazolo[1,5-a]pyridine,2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene;

wherein said cyclic ring is optionally substituted with one to threesubstituents selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl,acetylpiperazinyl, morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.

1. A compound of Formula X

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein n is 0, 1 or 2; and A is an aryl group or a heterocyclic group,wherein said heterocyclic group has 1 to 5 heteroatom ring membersindependently chosen from O, N, and S, and said heterocyclic group isaromatic or non-aromatic; and wherein said aryl group or saidheterocyclic group is optionally substituted with one or twosubstituents independently selected from the group consisting of C₁₋₃alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R; and R is asubstituted or unsubstituted cyclic ring, optionally containing 1 to 5heteroatom ring members independently chosen from O, N, and S, and saidcyclic ring is aromatic or non-aromatic.
 2. The compound, or astereoisomer thereof or a pharmaceutically acceptable salt thereof, ofclaim 1, wherein A is aryl optionally substituted with one or twosubstituents independently selected from the group consisting of C₁₋₃alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R.
 3. The compound, ora stereoisomer thereof or a pharmaceutically acceptable salt thereof, ofclaim 2, wherein A is phenyl substituted with one or two substituentsindependently selected from the group consisting of C₁₋₃ alkyl, halogen,benzyloxy, —R, —CH═CH—R, and —C≡C—R.
 4. The compound, or a stereoisomerthereof or a pharmaceutically acceptable salt thereof, of claim 1,wherein A is a heterocyclic group having 1 to 5 heteroatom ring memberschosen from O, N, and S; said heterocyclic group is aromatic ornon-aromatic; and said heterocyclic group is optionally substituted withone or two substituents independently selected from the group consistingof C₁₋₃ alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R.
 5. Thecompound, or a stereoisomer thereof or a pharmaceutically acceptablesalt thereof, of claim 4, wherein A is an aromatic heterocyclic grouphaving 1 to 5 heteroatom ring members chosen from O, N, and S; and saidaromatic heterocyclic group is optionally substituted with one or twosubstituents independently selected from the group consisting of C₁₋₃alkyl, halogen, benzyloxy, —R, —CH═CH—R, and —C≡C—R.
 6. The compound, ora stereoisomer thereof or a pharmaceutically acceptable salt thereof, ofclaim 5, wherein A is pyridine, pyrazine, or thiophene, wherein A isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₃ alkyl, halogen, benzyloxy,—R, —CH═CH—R, and —C≡C—R.
 7. The compound, or a stereoisomer thereof ora pharmaceutically acceptable salt thereof, of claim 1, wherein R is acyclic ring optionally containing 1-5 heteroatom ring members, and saidcyclic ring is optionally substituted with one to three substituentsindependently selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, (cycloalkyl)alkyl, benzyl, C₁₋₆ alkoxy,amino, mono- or di-C₁₋₆ alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆alkylcarbonylamino, mono- or di-C₁₋₆ alkylaminocarbonyl, mono- ordi-C₁₋₆ alkylaminosulfonyl, C₁₋₆ alkylsulfonyl, cycloalkylsulfonyl, C₁₋₆alkylcarbonyl, morpholinylcarbonyl, piperazinyl, acetylpiperazinyl,morpholinyl, pyrazolyl, C₁₋₆ alkylpyrazolyl, triazolyl, pyrrolidinonyl,and pyrrolidinyl.
 8. The compound, or a stereoisomer thereof or apharmaceutically acceptable salt thereof, of claim 1, wherein n is
 0. 9.The compound, or a stereoisomer thereof or a pharmaceutically acceptablesalt thereof, of claim 1, wherein n is
 1. 10. The compound, or astereoisomer thereof or a pharmaceutically acceptable salt thereof, ofclaim 1, wherein n is
 2. 11.-30. (canceled)
 31. The compound of claim 1of Formula 12

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and R² is a substitutedor unsubstituted aryl group or a substituted or unsubstituted heteroarylgroup, wherein said heteroaryl group has 1 to 5 heteroatom ring membersindependently chosen from O, N, and S. 32.-43. (canceled)
 44. Thecompound of claim 1 of Formula 13

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and R² is a substitutedor unsubstituted aralkoxy group, a substituted or unsubstituted arylgroup, or a substituted or unsubstituted heterocyclic group, whereinsaid heterocyclic group has 1 to 5 heteroatom ring members independentlychosen from O, N, and S, and said heterocyclic group is aromatic ornon-aromatic. 45.-60. (canceled)
 61. The compound of claim 1 of Formula14

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and R² is a substitutedor unsubstituted aryl or a substituted or unsubstituted heterocyclicgroup, wherein said heterocyclic group has 1 to 5 heteroatom ringmembers independently chosen from O, N, and S, and said heterocyclicgroup is aromatic or non-aromatic.
 62. The compound of claim 61 ofFormula 14a

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.63. The compound of claim 61 of Formula 14b

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.64. The compound of claim 61 of Formula 14c

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof.65.-77. (canceled)
 78. The compound of claim 1 of Formula 15

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen or C₁₋₆ alkyl; and R² is a substituted orunsubstituted aryl or a substituted or unsubstituted heteroaryl, whereinsaid heteroaryl group has 1 to 5 heteroatom ring members independentlychosen from O, N, and S group. 79.-87. (canceled)
 88. The compound ofclaim 1 of Formula 16

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R² is a substituted or unsubstituted aryl or a substituted orunsubstituted heteroaryl group, wherein said heteroaryl group has 1 to 5heteroatom ring members independently chosen from O, N, and S. 89.-97.(canceled)
 98. The compound of claim 1 of Formula 17

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and R² is a substitutedor unsubstituted aryl or a substituted or unsubstituted heterocyclicgroup, wherein said heterocyclic group has 1 to 5 heteroatom ringmembers independently chosen from O, N, and S, and said heterocyclicgroup is aromatic or non-aromatic. 99.-113. (canceled)
 114. The compoundof claim 1 of Formula 18

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and R² is a substitutedor unsubstituted aryl or a substituted or unsubstituted heteroarylgroup, wherein said heteroaryl group has 1 to 5 heteroatom ring membersindependently chosen from O, N, and S. 115.-126. (canceled)
 127. Thecompound of claim 1 of Formula 19

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and R² is a substitutedor unsubstituted aryl or a substituted or unsubstituted heteroarylgroup, wherein said heteroaryl group has 1 to 5 heteroatom ring membersindependently chosen from O, N, and S. 128.-139. (canceled)
 140. Thecompound of claim 1 of Formula 20

or a stereoisomer thereof or a pharmaceutically acceptable salt thereof;wherein R¹ is hydrogen, halogen, or C₁₋₆ alkyl; and R² is a substitutedor unsubstituted aryl or a substituted or unsubstituted heterocyclicgroup, wherein said heterocyclic group has 1 to 5 heteroatom ringmembers independently chosen from O, N, and S, and said heterocyclicgroup is aromatic or non-aromatic. 141.-155. (canceled)
 156. Apharmaceutical composition comprising the compound according to claim 1,or a stereoisomer thereof, or a pharmaceutically acceptable saltthereof, and at least one pharmaceutically acceptable excipient
 157. Amethod of inhibiting vascular adhesion protein-1 (VAP-1) in a mammal,comprising administering to the mammal, a therapeutically effectiveamount of the compound, or a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof according to claim
 1. 158. A method of treatingnonalcoholic hepatosteatosis (NASH) in a subject in need thereof, themethod comprising administering to the subject a therapeuticallyeffective amount of the compound according to claim 1, or a stereoisomerthereof, or a pharmaceutically acceptable salt thereof. 159.-163.(canceled)
 164. A method of treating a disease mediated by vascularadhesion protein-1 (VAP-1) in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effectiveamount of the compound according to claim 1, or a stereoisomer thereof,or a pharmaceutically acceptable salt thereof.
 165. The method of claim164, wherein the disease mediated by VAP-1 is selected from the groupconsisting of a lipid disorder, a lipoprotein disorder, condition ordisease which results from chronic fatty and fibrotic degeneration oforgans due to accumulated lipid and specifically triglycerideaccumulation and subsequent activation of a profibrotic pathway, Type Ior Type II Diabetes, clinical complications of Type I and Type IIDiabetes, chronic intrahepatic cholestatic condition, extrahepaticcholestatic condition, liver fibrosis, acute intraheptic cholestaticcondition, obstructive or chronic inflammatory disorder that arises outof improper bile composition, gastrointestinal condition with a reduceduptake of dietary fat and fat-soluble dietary vitamin, inflammatorybowel disease, obesity, metabolic syndrome, combined conditions ofdyslipidemia, diabetes and abnormally high body-mass index, persistentinfection by intracellular bacteria or parasitic protozoae,non-malignant hyperproliferative disorder, malignant hyperproliferativedisorder, colon adenocarcinoma and hepatocellular carcinoma, liversteatosis or associated syndromes, Hepatitis B infection, Hepatitis Cinfection, cholestatic and fibrotic effects that are associated withalcohol-induced cirrhosis or with viral-borne forms of hepatitis, liverfailure or liver malfunction as an outcome of chronic liver disease orof surgical liver resection, acute myocardial infarction, acute stroke,thrombosis which occurs as an endpoint of chronic obstructiveatherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, andcerebral infarction, individually or any combination thereof.
 166. Amethod of preparing a compound of Formula 1aa, or a stereoisomerthereof, or a pharmaceutically acceptable salt thereof,

the method comprising (a) reacting a compound of Formula 2 with acompound of Formula 3a or a compound of Formula 3b to obtain a compoundof Formula 1a

Z—R′  (Formula 3a)HC≡CR  (Formula 3b)

wherein Boc is an amine protecting group; n is 0, 1, or 2; A′ is phenyl,pyridine, pyrazine, thiophene, or benzothiophene; wherein said phenyl,pyridine, pyrazine, thiophene, or benzothiophene is optionallysubstituted with C₁₋₃ alkyl or halogen; Z is boronic acid (B(OH)₂) orboronic acid pinacol ester; R′ is —R, —CH═CH—R, or —C≡C—R; and R is asubstituted or unsubstituted cyclic ring, optionally containing 1 to 5heteroatom ring members chosen from O, N, e and S, and said cyclic ringis aromatic or non-aromatic; and (b) removing Boc from the compound ofFormula 1a under reaction conditions to obtain the compound of Formula1aa, or the stereoisomer thereof, or the pharmaceutically acceptablesalt thereof.
 167. The method of claim 166, wherein the cyclic ring isselected from the group consisting of benzene, pyridine,tetrahydropyridine, pyridin-2-one, pyrimidine, imidazole, pyrazole,benzodioxole, benzoxadiazole, benzothiazole, indazole,1,3-dihydroindol-2-one, quinolin-2-one, 3,4-dihydroisoquinolin-1-one,3,4-dihydroquinolin-2-one, 3,4-dihydro-1,4-benzoxazine,2,3-dihydro-1,4-benzoxazine, 1,4-benzoxazin-3-one,1,4-dihydro-3,1-benzoxazin-2-one, 5,6,7,8-tetrahydronaphthyridine,triazolo[1,5-a]pyridine, 2,3-dihydro-pyrido[2,3-b][1,4]oxazine,3,4-dihydro-pyrido[3,2-b][1,4]oxazine, pyrido[2,3-b][1,4]oxazin-2-one,pyrido[3,2-b][1,4]oxazin-3-one, 1,4-dihydroquinazolin-2-one,1H-pyrrolo[2,3-b]pyridine, benzoxazole, and thiophene; wherein saidcyclic ring is optionally substituted with one to three substituentsindependently selected from the group consisting of halogen, C₁₋₆ alkyl,difluoromethyl, trifluoromethyl, C₁₋₆ alkoxy, amino, mono- or di-C₁₋₆alkylamino, C₁₋₆ alkoxy-C₁₋₆ alkylamino, C₁₋₆ alkylcarbonylamino, mono-or di-C₁₋₆ alkylaminocarbonyl, mono- or di-C₁₋₆ alkylaminosulfonyl, C₁₋₆alkylsulfonyl, C₁₋₆ alkylcarbonyl, morpholinylcarbonyl, piperazinyl,acetylpiperazinyl, morpholinyl, pyrazolyl, triazolyl, and pyrrolidinyl.168. A method of treating nonalcoholic hepatosteatosis (NASH) in asubject in need thereof, the method comprising administering to thesubject a therapeutically effective amount of the pharmaceuticalcomposition according to claim
 156. 169. A method of treating a diseasemediated by vascular adhesion protein-1 (VAP-1) in a subject in needthereof, the method comprising administering to the subject atherapeutically effective amount of the pharmaceutical compositionaccording to claim
 156. 170. The method of claim 169, wherein thedisease mediated by VAP-1 is selected from the group consisting of alipid disorder, lipoprotein disorder, condition or disease which resultsfrom chronic fatty or fibrotic degeneration of organs due to accumulatedlipid, triglyceride accumulation and subsequent activation of aprofibrotic pathway, Type I Diabetes, Type II Diabetes, complication ofType I or Type II Diabetes, chronic intrahepatic cholestatic condition,extrahepatic cholestatic condition, liver fibrosis, acute intrahepticcholestatic condition, obstructive or chronic inflammatory disorder thatarises out of improper bile composition, gastrointestinal condition witha reduced uptake of dietary fat or fat-soluble dietary vitamin,inflammatory bowel disease, obesity, metabolic syndrome, combinedconditions of dyslipidemia, diabetes and abnormally high body-massindex, persistent infection by intracellular bacteria or parasiticprotozoae, non-malignant hyperproliferative disorder, malignanthyperproliferative disorder, colon adenocarcinoma and hepatocellularcarcinoma, liver steatosis or associated syndrome, Hepatitis Binfection, Hepatitis C infection, cholestatic and fibrotic effects thatare associated with alcohol-induced cirrhosis or with viral-borne formsof hepatitis, liver failure or liver malfunction as an outcome of achronic liver disease or of surgical liver resection, acute myocardialinfarction, acute stroke, thrombosis which occurs as an endpoint ofchronic obstructive atherosclerosis, osteoarthritis, rheumatoidarthritis, psoriasis, and cerebral infarction, individually or anycombination thereof.